Nbrc.ac.in
Annual Report 2012-13
National Brain Research Centre
Manesar, Haryana (India)
Mandate .
From the Director's Desk .
Research Reports . 01
Molecular & Cellular Neuroscience Division . 03
• Prof. Subrata Sinha .
• Dr. Nihar Ranjan Jana .
• Dr. Pankaj Seth .
• Dr. Ellora Sen .
• Dr. Shiv K Sharma .
• Dr. Anirban Basu .
• Dr. Ranjit Kumar Giri .
• Dr. Sourav Banerjee .
• Dr. Sayali Ranade .
Systems & Cognitive Neuroscience Division . 35
• Prof. Neeraj Jain .
• Dr. Soumya Iyengar .
• Dr. Narender K. Dhingra .
• Dr. Yoganarasimha Doreswamy .
Computational Neuroscience & Neuroimaging Division . 51
• Dr. Nandini Chatterjee Singh .
• Prof. Prasun Kumar Roy .
• Dr. Pravat Kumar Mandal .
Publications & Patents . 67
Presentations . 71
Distinctions, Honours & Awards . 77
Externally Funded Research Projects . 81
Core Facilities . 87
• Distributed Information Centre (DIC) .
• Animal Facility.
DBT's Electronic Library Consortium (DeLCON) . 93
National Neuroimaging Facility . 97
Translational Research : Clinical Unit . 101
Meeting and Workshop . 105
International Collaborations & Networking . 109
• International Collaborations . 111
• Networking . 111
Invited Lectures . 113
Academic Programmes . 117
• Ph.D. in Neuroscience . 119
• Integrated Ph.D. in Neuroscience . 119
• Summer Training & Short Term Programmes . 119
General & Academic Administration - A Profile . 121
Institutional Governance Structure & People at NBRC . 125
Annual Financial Statements . 137
Mandate & Objectives
different regions of the country for efficient achievement
• Pursue basic research to understand brain function in
of the objectives of the Center.
health and disease.
• To collect, assimilate, publish and disseminate data and
• Generate trained human resources with the capability
information on relevant aspects of neuroscience to the
to carry out inter-disciplinary research in neuroscience.
• Promote neuroscience in India through networking
• To establish, operate and maintain state-of-the-art
among institutions across the country.
facilities as well as databases for carrying research and
development activities and make such facilities and
databases available to scientists and researchers from
all over the country and abroad.
• To undertake, aid, promote, guide and coordinate
research of high caliber in basic and clinical
• To provide for instructions and training in such other
neuroscience related to diseases and disorders of the
branches of learning as the Centre may deem fit.
nervous system.
• To provide facilities for the advancement of research and
• To develop NBRC as the national apex centre for
development to facilitate learning and dissemination of
neuroscience research and promote neuroscience
research at different centres in the country and to
provide consulting services to other institutions,
programmes and field outreach activities to contribute
agencies and industries.
to the development of society.
• To promote, encourage and augment effective
• To promote, develop, collaborate or otherwise assist in
linkages, alliances and affiliations between the Centre
providing services of research, training, consulting or
and National and International Scientific and Research
guidance related to neurosciences activities comprising
Institutions, bodies, agencies/laboratories and other
biological, psychological, sociological and clinical
organizations working in the field of brain and
• To do all such other acts and things as may be necessary
• To establish one or more satellite centers to serve
or desirable to further the objectives of the Centre.
National Brain Research Centre
From the Director's Desk
The National Brain Research is one of the very few centres
Research from another group which works on the Japanese
that has the entire spectrum of neuroscience research under
Encephalitis Virus (JEV) has provided important insights into
one roof. Though, for purposes of convenience it could
JEV-induced neuropathology. They have demonstrated
be said to have research groups in molecular and cellular
that JEV infection is more robust in undifferentiated Neural
neuroscience, systems neuroscience, neuro-imaging and
Stem Progenitor Cells (NSPCs) compared to differentiated
computational and clinical neuroscience, the frontiers of
ones. Further, JEV infected NSPCs show hampered
each research area extend far beyond the limitations set out
differentiation and arrested migration in adherent
by these functional boundaries. Our endeavour in NBRC is
neurosphere cultures. Interestingly, they have also shown
to ask fundamental scientific questions that enhance the
that neuronal differentiation appears to be more severely
horizons of our understanding and to then translate new
affected by JEV compared to astrocyte differentiation
knowledge to public good. As we struggle in our effort to
and that transcription factors involved in both neuronal
transform the incremental to the revolutionary, our effort
and astrocyte differentiations are significantly decreased
has been to strive for excellence. India struggles with the
following JEV infection.
social and demographic battles of both a developing and a
developed society – neither does the past let go so easily,
One of the research groups at NBRC which has been working
eg. in terms of neonatal hypoxia and brain infections, nor
on the pathogenesis of neurodegenerative diseases has
created brain Ube3a-deficient Huntington's disease (HD)
are we free of the attendant problems of a longer life span
transgenic mice that manifest severe disease pathology
in terms of degenerative diseases and dementias. As the
and early death compared to HD mice. This group has also
only research institute in the country dedicated to the brain,
identified neuronatin as a novel substrate of the ubiquitin
we have a unique responsibility of towards increasing our
ligase malin in Lafora disease and has demonstrated that
basic understanding of neuroscience, as well as finding
neuronatin mediated aberrant calcium signalling plays a
ways of ameliorating disorders of the brain.
crucial role in the pathogenesis of Lafora disease.
At NBRC, the neuro AIDS laboratory is focusing its research
Another research group has developed a novel in vitro
efforts to decipher intricacies of neuron-glia interactions
model of Alzheimer's disease (AD) using CNS stem cell
following exposure to HIV-1 Tat using a human fetal brain
cultures which manifests beta amyloidopathies similar
derived neural stem cell culture system. Live cell imaging
to animal models of AD except plaque formation. This
techniques are being used to evaluate the role of HIV-1
group has further reported that a novel anti-cancer drug,
Tat on alterations of intracellular calcium in glial cells,
8-Methoxypyrimido [49,59:4,5] thieno(2,3-b) Quinoline-
particularly astrocytes, and its relation to neuron damage.
4(3H)-One (MPTQ) can inhibit the growth of neuroblastoma
The laboratory is also actively engaged in understanding
cells. For the first time, they have also demonstrated the
cellular and molecular pathways possibly involved in HIV-1
molecular mechanisms associated with MPTQ-mediated
and drugs of abuse induced co-morbidity.
cell death in neuroblastomas.
National Brain Research Centre
Ongoing research on brain tumours (glioblastoma
to normal speech. This suggests that music processing
multiforme) at NBRC has identified -defensin 3 as a
pathways may be preserved in autism. Given that verbal
negatively regulator of HLA-G expression in glioma cells.
communication or speech is often impaired in children with
As HLA-G constitutes a way for gliomas to escape from
autism, these findings suggest that musical speech may
immune-surveillance, this finding may be of direct clinical
prove to be beneficial in improving verbal communication
relevance in the modulation of immune escape mechanisms
in glioma. By demonstrating how (i) JNK-NFB axis regulates
resistance to TNF induced apoptosis (ii) Ras/NFB axis
A number of cutting-edge techniques for imaging the
sensitizes glioma cells to Sonic-hedgehog inhibitor
human brain have been developed recently at NBRC which
induced death, this research group has analyzed pathways
are of special importance for those suffering from brain
that lead to glioma progression and also suggested ways
diseases. The group specializing in Neurospectroscopy
for combating the same. This research group has also been
has established novel non-invasive imaging techniques to
granted a European patent on the bicyclic triterpenoid
correlate brain oxidative stress and brain pH (combined) in
Iripallidal which may have therapeutic potential as a novel
patients diagnosed with mild cognitive impairment and
anti-glioma and anti-neoplastic therapy in vitro in 2013.
Research on the molecular basis of learning and memory
MRI-based Elastometric relaxation mapping has been used
had earlier shown that acetylation level of alpha tubulin
by another research group to track the ageing process in
in the hippocampus is enhanced in an activity-dependent
the brain, especially in Alzheimer's disease, who found that
manner. They have recently begun investigating the
temporal elasticity relaxation coefficient of the parenchyma
molecular mechanisms of alpha tubulin acetylation and
is an effective temporal rate index that can act as a brain
have found that increasing acetylation levels enhances
ageing biomarker. This group has also explored the
glutamate receptors on the cell membrane. Since
feasibility of using a preclinical rodent model for MRI and
glutamate receptor trafficking plays important roles in
immunohistochemical studies, to enable the determination
synaptic plasticity related to memory, these results suggest
of the process kinetics of endogenous neurogenesis
that acetylation regulates this process and thus contributes
and synaptogenesis in cerebral stroke. In this model,
to synaptic plasticity and memory.
diffusion imaging and allometric analysis have been used
to delineate the time duration required for neuroblasts to
One of the laboratories at NBRC is interested in under
move from the subventricular zone to the stroke penumbra
standing mechanisms of brain reorganization following
zone, which can then be used to plan pharmacological
spinal cord injuries. This research group has found that
interventions for neurogenesis and synaptogenesis, so that
large-scale brain reorganization is not mediated by cortical
optimal neural recovery occurs.
mechanisms. Their findings suggest that changes in the
cortex following spinal cord injuries are likely mediated by
NBRC is pleased to welcome a new faculty member, Dr.
reorganization at the medullary level, which is also a site for
Arpan Bannerjee, who joined us this year. He plans to
use a diverse set of techniques which include building
theoretical models of the brain and behaviour, developing
The research group that is interested in neuroethology has
signal processing algorithms to study brain network
been studying how brain structure and function relates to
mechanisms and using functional brain imaging techniques
behaviour in crows which are known to perform certain
(Electroencephalography and Magnetoencephalography)
cognitive tasks on part with non-human primates. They
to understand the neurodynamics of decision making, the
have used histology and immunohistochemistry to study
neural basis of speech processing, multisensory processing
the dopaminergic system in these birds, which is known to
and developing neuro-markers for brain disorders.
be involved in cognition. They have shown for the first time
that the hyperpallium, a part of the avian cortex contains a
In addition to research, NBRC is an educational centre
dense plexus of TH-positive fibers. These findings suggest
and continues its activities as a Deemed University.
that this brain region may be important for the remarkable
As of March 31st, 2013, NBRC has awarded the degree
cognitive abilities of corvids.
of Doctor of Philosophy in Neuroscience to 36 students.
NBRC also provides hands-on training to a number of
Research on speech and language at NBRC has demon-
summer trainees (selected by the Indian Academy of
strated that children with autism across the spectrum
Science, Bangalore, Indian National Science Academy,
show strong neural activity for sung speech as compared
New Delhi and National Academy of Sciences, Allahabad),
National Brain Research Centre
to encourage them to pursue Neuroscience as a career.
with talks on neuroscience presented by Prof. NR Jana
NBRC celebrated its 9th Foundation Day on 16 December,
(Amity University, Manesar) and postdoctoral fellows,
2012 by inviting students from five schools in Gurgaon /
Dr. Chaitra Rao (Government Senior Secondary School,
Manesar to attend a lecture on Neuroscience, a scientific
Pachgaon) and Dr. Nabonita Sengupta (Kendriya Vidyalaya,
poster presentation, demonstrations and quiz on its
NSG, Manesar).
campus conducted by NBRC students. A major highlight
of NBRC's Foundation Day celebrations was a public lecture
To promote awareness about neuroscience and networking
entitled "Stem Cells and Disorders of the Brain: What have
between different institutions involved in the discipline
we learned?" by the distinguished neuroscientist Professor
across India, NBRC sponsored the Brain Awareness Week
Mahendra S. Rao (Director, Centre for Regenerative
in different institutions across the country. Under the aegis
Medicine National Institute of Health, Bethesda, USA) who
of the Brain Awareness Week, talks, poster sessions and
specializes in the use of human embryonic stem cells (hESCs)
demonstrations were organized at the Regional Science City,
and other somatic stem cells in regenerative therapies.
Lucknow, Banaras Hindu University, AIIMS, Bhubaneswar,
Besides academics and research, NBRC also encourages
Jawaharlal Nehru University, New Delhi, CDRI, Lucknow
extra-curricular activities. NBRC's month-long annual
and IIIT, Allahabad to educate the general public about
festival Tantrika is unique in that it combines scientific
the brain and various disease processes that can affect it.
events as well as sports, arts and crafts and is organized
The dual purpose served by the Brain Awareness Week is to
almost entirely by students of NBRC. This year's highlights
educate students (at school and college levels) about the
included a talk entitled "Tum Vahaan, Mein Yahaan, Naseeb
brain and to motivate them to pursue neuroscience as a
Apne Apne: The effect of Position on Cell Fate" by the
career option.
noted neuroscientist Dr. Shubha Tole (TIFR, Mumbai) and
a scientific poster presentation for NBRC students. For the
The phrase "Molecules to behaviour' has been used so many
first time, students took the initiative to organize a Blood
times that it has become a cliché. However, like all clichés
Donation Camp with the Red Cross Society of India on
it succinctly expresses a kernel of truth that is central to the
campus during Tantrika.
dreams of all neuroscience researchers. We hope that in the
coming year the incipient scientific dreams of all scientists
As a part of its community outreach programmes, NBRC
and students at NBRC come one step closer to fruition and
also celebrated the National Science Day (to celebrate the
we would take one step forward in this uncharted journey
Nobel Laureate CV Raman's birthday, 28 February, 2012)
towards unraveling the complexities of our last frontier.
Prof. Subrata Sinha
National Brain Research Centre
Molecular & Cellular Neuroscience Division
Systems & Cognitive Neuroscience Division
Computational Neuroscience & Neuroimaging Division
Molecular & Cellular
Prof. Subrata Sinha
Dr. Nihar Ranjan Jana
Dr. Shiv Kumar Sharma
Dr. Anirban Basu
Dr. Ranjit Kumar Giri
Dr. Sourav Banerjee
Dr. Sayali Ranade
THERAPY OF GLIOMA:
Principal Investigator
Subrata Sinha
AND ABERRANT GENE
Work continues on the response of glioma to therapy, and
reducing c-Jun expression and phosphorylation. This
how hypoxia affects this response. Glioma are among the
attenuation was relieved by increased FAT1 expression in
most hypoxic of all tumours and hypoxia-necrosis cycle is
the high grade glioma cell lines. The results were confirmed
a hallmark of Glioblastoma multiforme (GBM), the most
by simultaneously knocking down FAT1 and PDCD4. The
malignant of glial tumours. Hypoxia and inflammation
molecules that were increased due to high Fat1 expression
are closely linked. Cytokines mediating inflammation may
included MMP3, VEGF, PLAU, the pro-inflammatory
promote tumour growth by either facilitating a conducive
regulator COX-2 and cytokines IL1β and IL-6.
host microenvironment for the tumour, as well as by acting
as autocrine growth factors. There are several mechanisms
These results were validated in 35 primary human WHO
leading to the dysregulation of the inflammatory
grade IV Glioblastoma multiforme samples. There was
microenvironment in tumours. In collaboration with Dr.
a marked variation in FAT1 expression within the same
Kunzang Chosdol, Department of Biochemistry, AIIMS, we
histological grade. There was a significant negative
have identified a novel link between inflammation and
correlation between the expression of FAT1 and PDCD4
(p= 0.0145) and a positive correlation with COX 2 (p=0.048).
For IL6 there was a similar positive trend, though it was
Our initial work on identifying differences between tumour
not statistically significant. The results, which validate the
and corresponding normal DNA by profiling differences in
in-vitro findings, indicate that there may be a possible
their DNA fingerprinting patterns had identified a region
explanation for the manifestation of heterogeneity of the
in the chromosomal region 4q34 – 35, as being altered in
inflammatory response within Glioblastoma multiforme.
a significant proportion of glial tumours. Analysis of LOH
There have been several attempts to sub-classify this
profiles indicated that it harboured a tumour suppressor
histological grade in an attempt to associate molecular
gene (TSG), the most likely being the human homologue of
pathways with tumour behaviour and prognosis. FAT1 and
the Drosophila TSG FAT 1 (Chosdol et al 2009). However, in
inflammation could be amongst the parameters that may
an apparent contradiction, this gene was highly expressed
be taken into account for this purpose.
in glial tumour cell lines derived from high grade tumours
but not in those derived from low grade ones. Knock down
This novel pathway for inflammation is being studied in
of this gene by siRNA resulted in reduced cell migration
the context of its role in the activation of inflammatory
and invasion in the high grade glioma cells, though it
responses in hypoxia. Work is in progress on how hypoxia
did not affect proliferation. Microarray analysis of the
affects the expression of FAT1 and its differential role in
knockdown indicated an inverse relationship with the TSG,
hypoxia and normoxia. The association of FAT1 expression
PDCD4 (Programmed Cell Death 4), which was increased
with the markers of the hypoxic response in primary human
by this knock down. PDCD4 inhibited AP1 activation by
tumours would also be studied.
National Brain Research Centre
associated phenotype and the processes linking the same
1. Dikshit B, Irshad K, Madan E, Aggarwal N, Sarkar C,
and also as a biomarker for the above processes (PCT/
Chandra PS, Gupta DK, Chattopadhyay P, Sinha S,
IB2013/050086, filed on 4 Jan 2013). (Jointly by DBT, AIIMS
Chosdol K. FAT1 acts as an upstream regulator of
oncogenic and inflammatory pathways, via PDCD4, in
glioma cells. Oncogene advance online publication,
17 September 2012; doi: 10.1038/onc.2012.393 (joint
1. Dr Kunzang Chosdol (Biochemistry), Dr Parthaprasad
Chattopadhyay (Biochemistry), Dr Chitra Sarkar
(Pathology), Dr. P S Chandra (Neurosurgery) and Dr
Deepak Gupta (Neurosurgery), AIIMS
Use of the FAT1 gene and its products, including RNA,
2. Dr Tapasya Srivastava, University of Delhi, South
protein and the derivatives of the same, as suitable
molecule/s for either inflammation or cancer and the
3. Dr Ellora Sen, NBRC
National Brain Research Centre
Principal Investigator
Subrata Sinha
THERAPEUTIC AGENTS:
TARGETING TUMOURS
THROUGH PLACENTAL
ALKALINE PHOSPHATASE
Alkaline phosphatase (AP) has 4 major isozymes: (1) Tissue
a fragment a transmembrane Sendai virus F protein. The
non specific (TNAP) (2) Intestinal (IAP) (3) Placental (PAP)
virosome could deliver a drug payload (Doxorubicin), that
(4) Placental like or germ cell alkaline phosphatase (PLAP/
resulted in enhanced death of the PAP expressing cells.
GCAP). Of these the PAP and PAP/GCAP isozymes have been
We have now been able to show that the combination of
shown to be expressed ectopically in a number of tumours,
recombinant antibody based targeting with the Sendai
hence would come under the category of Onco-placental
virosome delivery system is able to specially deliver
antigens. While all the AP isozymes have considerable
the payload to the cytoplasm of cells expressing PAP.
homology, PAP and PLAP/GCAP are very highly homologous
Antibody based targeted delivery is often directed to the
and are immunologically indistinguishable. While both PAP
endosomal compartment, resulting in degradation of
and PLAP/GCAP are highly expressed in germ cell tumours,
the payload as well as increased immunogenicity of any
these are also expressed in a variety of cancers, including
protein component of the same. However, it has been
cervix, breast etc.
earlier shown by our collaborators that the F protein on the
Sendai virosome is able to mediate membrane fusion which
Germ cell tumours comprise of 2 to 10% of childhood
results in cytoplasmic delivery of most of the components
brain tumours. In addition, PAP is expressed on tumours
being carried. We have demonstrated that the Sendai
metastatic to the brain, depending on tumour type.
immunovirosome generated in this study is specifically able
to target PAP expressing cells and also results in about 75%
The work aims to develop a tumour specific targeting
cytoplasmic delivery. This would translate into increased
modality using a combination of: (1) Recombinant isozyme
efficacy as well as lower immunogenicity.
specific antibodies of human origin that can specifically
target PAP or PLAP/GCAP but not the other constitutively
Use of PLAP/GCAP promoter for specific gene expression
expressed isozymes. (2) using PLAP/GCAP promoters
within tumour cells: This is intended to bring about a
for (a) specific prodrug activation within tumour cells for
dual level of specificity as the promoter is only active in
expression of exogenous prodrug drug metabolizing genes
cell lines that express PLAP. The PLAP/GCAP promoter
or (b) for expression of TGS inducing dsRNA. This approach
was coupled with an NF kappaB enhancer. The promoter/
would utilise a particulate delivery system (till now the
promoter-enhancer activities were assayed by various
Sendai virosome system) for targeted delivery.
reporter systems in a battery of cell lines along with their
appropriate controls. The utility of these constructs for gene
Earlier we had been successful specific particulate delivery
dependent enzyme prodrug therapy (GDEPT) was studied
vehicle (Sendai immunovirosome), that is able to bind
upon and preliminary results revealed the activation of the
specifically to PLAP expressing cells. This was because of
inactive form of drug 5-fluorocytosine to its active form
an engineered recombinant scFv fragment, oriented on
5-fluorouracil by the enzyme cytosine deaminase, when
the virosome surface based its surface by the fusion with
its expression was governed by PLAP promoter/enhancer
National Brain Research Centre
systems. This resulted in significant enhancement of cell
1. Kumar R, Andrabi R, Tiwari A, Sankaran S.P, Wig N,
Dutta D, Sankhyan A, Khan L, Sinha S, Luthra K. A novel
Work is also ongoing in developing recombinant
strategy for efficient production of anti-V3 human
antibody based approaches for generating neutralizing
scFvs against HIV-1 clade C, BMC Biotechnology Online
antibodies to HIV. Both viruses have central nervous
Publication, 15 November 2012; doi:10.1186/1472-
system effects. Hepatitis encephalopathy is seen in a
6750-12-87 (joint corresponding author)
large proportion of ICU admissions in most hospitals. HIV
encephalopathy is also a problem especially for long term
2. Andrabi, R, Kumar R, Bala M, Nair A, Biswas A, Wig
survivors on anti HIV drugs. Our work has been to generate
N, Kumar P, Pal R, Sinha S, Luthra K. Production
recombinant antibody libraries from EBV transformed B cell
and characterization of human anti-V3 monoclonal
lines, which secreted specific neutralizing antibodies to the
antibodies from the cells of HIV-1 infected Indian
HIV Clade C which is the commonest Clade in India and is
donors. Virology Journal 2012, 9:196
comparatively less studied than Clade B viruses. This is also a new strategy for generating scFv antibodies from pre-
selected EBV transformed lines, which results in a directed
1. Dr. Parthaprasad Chattopadhyay, Dr. Kunzang Chosdol
library which has a higher proportion of the desired
and Dr. Kalpana Luthra, (Biochemistry), AIIMS
antibodies than a conventional library from peripheral
2. Prof. Debi P Sarkar, Dept. of Biochmistry, University of
lymphocytes of patients.
Delhi, South Campus
National Brain Research Centre
UNDERSTANDING THE
Principal Investigator
Nihar Ranjan Jana
Post Doctoral Fellows
AUTISM AND AUTISM
Supriya Bhavnani, Ruchi Gaur
Research Fellows
SPECTRUM DISORDERS
Swetha K. Godavarthi, Megha Maheswari,
ASSOCIATED UBIQUITIN
Project Assistants
Rajarshi Mukherjee, Anirudha Das
LIGASE, UBE3A/E6-AP
Technical Assistants
Ankit Sharma, Mahendra Singh
E6-AP protein encoded by UBE3A gene was first identified as
ticoid receptor signalling in hippocampus could lead to
a cellular protein linked in ubiquitin-mediated proteolysis of
chronic stress and increased anxiety-like behaviour in AS
tumor suppressor p53 in assistance with E6 oncoprotein of
mice (Ube3a-maternal deficient mice). Chronic stress also
the human papilloma virus. Subsequently, it is characterized
could be associated with learning and memory impairment
as a HECT (homologous to E6-AP C terminus) domain family
in these mice. We have now tested the role of fluoxetine
of E3 ubiquitin ligase, an important enzyme involved in
(a selective serotonin reuptake inhibitor) on resetting
targeting protein for ubiquitination. Ube3a also acts as a
of HPA axis and recovery of anxiety-like behaviour in AS
transcriptional co-activator of steroid hormone receptors.
mice. Chronic treatment of fluoxetine partially rescued
Ube3a shows neuron specific imprinting and dysfunction
the expression of GR in the hippocampus along with GR
of maternally inherited Ube3a causes Angelman syndrome
target proteins like BDNF, SGK and FKBP5 and also restored
(AS). AS is a neurodevelopmental disorder characterized by
HPA axis as seen by normalization of blood corticosterone
severe mental retardation, speech impairment, vulnerability
level in AS mice. The anxiety-like behaviour also partially
to seizures, ataxia and unique behavioural features such
recovered upon fluoxetine treatment as evident from
as improper laughter and autistic features. Copy number
the open field and light-dark box tests. Presently, we are
variation of the UBE3A gene (duplication) also reported
testing the role of enriched environment in the recovery of
in autism. Ube3a maternal deficient mice exhibit many
learning and memory deficits in AS mice.
features of AS, including cognitive and motor dysfunction.
These mice also display defects in hippocampal LTP, altered
Earlier we have demonstrated that Ube3a function as a
function of hippocampal CAMK-IIα and abnormal dendritic
cellular protein quality control ubiquitin ligase. We have
spine morphology. Studies in these mice also provided
also demonstrated that the partial loss of function of Ube3a
further hint that Ube3a is necessary for development of
might be associated with abnormal synaptic function in
synapse, experience-dependent cortical plasticity and
HD transgenic mice brain. In order obtain further insight
maturation of neocortex.
of the role of Ube3a in HD pathogenesis, we created brain
Ube3a deficient HD transgenic mice. Male HD mice were
Past several years we are engaged in exploring the
crossed with Ube3a-maternal deficient (m-/p+) female
physiological function of Ube3a and how its defect could
to obtain brain Ube3a-deficient HD mice. It is important
lead to AS. We are particularly interested in (1) identification
to note that paternally expressed Ube3a in imprinted in
and functional characterization of novel substrates of
brain and Ube3a-maternal deficient mice exhibits loss of
Ube3a, (2) molecular mechanism of cognitive impairment
Ube3a expression in brain. Interestingly, we observed that
in AS mice model, and (3) role of Ube3a in the progression
the disease progression (onset and severity) was much
of Huntington's disease.
faster in Ube3a-deficient HD mice in comparison with
only HD mice. Ube3a-deficient HD mice also dies much
Recently, we have demonstrated that deranged glucocor-
earlier compared to HD mice (Fig.1). Ube3a-deficient HD
National Brain Research Centre
mice manifest motor abnormalities as early as 5 weeks old,
2. D. Chhangani, N.R. Jana and A. Mishra (2013).
when HD mice behaves like wild type mice. However, by
Misfolded Proteins Recognition Strategies of E3
7-8 weeks, Ube3a-deficient HD mice shows severe motor
Ubiquitin Ligases and Neurodegenerative Diseases.
problems and during this age HD mice begin to exhibits
Molecular Neurobiology, 47, 302-312.
motor problems. These mice also showed frequent seizure
3. A. Mishra, M. Maheshwari, D. Chhangani, N. Fujimori,
that often leads to death. Total brain weight and the
F. Endo, A. P. Joshi, N. R. Jana and K. Yamanaka
straital volume were significantly reduced in these mice
(2013). E6-AP association promotes SOD1 aggresomes
at 7-8 weeks of age compared to age-matched HD mice.
degradation and suppresses toxicity. Neurobiology of
No apoptotic cell death was detected in the straitum and
Aging, 4, 1310, e11-23.
other brain regions and there was no sign of inflammation.
4. M. Maheshwari, A. Samanta, S. K. Godavarthi, R.
Immunohistochemical staining revealed increased mutant
Mukherjee, and N.R. Jana (2012). Dysfunction of the
huntingtin aggregate load in Ube3a-deficient HD mice
Ubiquitin Ligase Ube3a May Be Associated with Synaptic
brain compared to HD mice at 7-8 weeks age. Currently,
Pathophysiology in a Mouse Model of Huntington
we are investigating the probable cause of early neuronal
Disease. Journal of Biological Chemistry, 287, 29949-
dysfunction in Ube3a-deficient HD mice.
Presentations
1. A.Das, S. Bhutani, M. Maheshwari, S. C. Lakhotia and
N. R. Jana. Dysregulation of core components of SCF
complex in polyglutamine disorders. Annual Meeting
of Society for Biological Chemists (SBCI), Kolkata, 2012.
2. N. R. Jana. Involvement of Ube3a in cellular protein
quality control: Implication in protein misfolding
neurodegenerative disorders. NEUROCON, Kolkata,
3. N. R. Jana. Role of ubiquitin ligase Ube3a in the
pathogenesis of Huntington's disease. Annual Meeting
of the Society for Neurochemistry, India (SNCI), 2013.
Funding
1. Study the defect in neurogenesis and initial synapse
formation in mouse model of Angelman mental
Figure1. Ube3a-deficient HD transgenic mice exhibits
retardation syndrome. Council of Scientific and
shorter life-span. A) Cross breeding, genotyping of mice and
Industrial Research. Govt. of India., Grant No:
immunoblot analysis. B) Life-span of wild-type,
37(1408)/10/EMR-II dt. 25-06-2010
Ube3a-maternal deficient, HD and Ube3a-maternal deficient
HD mice. C) Ube3a-deficient HD mice exhibits drastic
2. Role of E6-AP in the progression of Huntington's disease.
decrease in body weight.
Department of Biotechnology, Govt. of India (National
Bioscience Award for Career Development). Grant No:
BT/HRD/34/18/2008 dt. 16-04-2010.
1. S. Bhutani, A. Das, M. Maheshwari, S.C. Lakhotia and
I. Dr. Nobuyuki Nukina, RIKEN Brain Science Institute,
N.R. Jana (2012). Dysregulation of core components
of SCF complex in polyglutamine disorders. Cell Death
II. Dr. Nikhil Jana, Indian Association for the Cultivation of
and Disease, 3, e428.
Sciences, Kolkata.
National Brain Research Centre
Principal Investigator
Nihar Ranjan Jana
THE PHYSIOLOGICAL
Post Doctoral Fellows
FUNCTION OF MALIN,
Supriya Bhavnani, Ruchi Gaur
Research Fellows
A UBIQUITIN LIGASE
Swetha K. Godavarthi, Megha Maheswari,
MUTATED IN LAFORA'S
Project Assistants
Rajarshi Mukherjee, Anirudha Das
Technical Assistants
Ankit Sharma, Mahendra Singh
MYOCLONUS EPILEPSY
Lafora disease (LD) is an inherited (autosomal recessive)
is hypothesized that the altered clearance of substrates
progressive myoclonus epilepsy, usually evident during
of malin might lead to disease pathogenesis. Therefore,
teenage and patient dies within first decade of disease
identification of substrates of malin could open a new
onset. The disease is clinically characterized by progressive
opportunity in understanding the pathogenesis of LD.
increase in myoclonic and visual seizures, dementia,
In the proposed project, we are trying to identify and
psychoses, muscles wasting leading the patient into a
exemplify the novel substrates of malin. In addition, we are
vegetative state and ultimately death. Cytopathological
also exploring the role of intracellular protein degradation
features of LD include intracellular accumulation of
pathways in LD pathogenesis.
insoluble polyglucosan bodies (known as Lafora bodies)
and widespread neurodegeneration. Lafora bodies are
Earlier we have shown malin interacts with neuronatin
not only observed in brain but also in other non-neuronal
and promotes its proteasome-mediated degradation.
tissues like liver, heart, skeletal muscle, skin etc.
Malin also negatively regulates neuronatin-stimulated
glycogen synthesis. Now we demonstrate that the
LD is caused by mutations in the EPM2A or EPM2B
level of neuronatin is significantly up-regulated in the
(NHLRC1) genes encoding laforin (a protein phosphatase)
skin biopsy sample of LD patients having mutations in
and malin (a E3 ubiquitin ligase) respectively. Patients
both malin and laforin. Neuronatin is highly expressed
with mutations in either laforin or malin are clinically
in human fetal brain with gradual decrease in expression
and pathologically indistinguishable, signifying that
in developing and adult brain. However, in adult brain,
both proteins work together in some common signalling
neuronatin is predominantly expressed in parvalbumin-
cascades and deficiency in those pathways could lead to
positive GABAergic interneurons and localized in their
disease appearance. Emerging proof indicates that both
processes. The level of neuronatin is increased and
laforin and malin could play a significant role in regulating
accumulated as insoluble aggregates in the cortical area of
glycogen metabolism and autophagy. Knockout mice
LD brain biopsy samples and there is also a dramatic loss
for both laforin and malin also display progressive
of parvalbumin-positive GABAergic interneurons (Fig.2).
accumulation of Lafora bodies in various tissues including
Ectopic expression of neuronatin in cultured neuronal
brain, defects in autophagic degradation pathway and
cells result in increased intracellular Ca2+, endoplasmic
extensive neurodegeneration. But how Lafora bodies
reticulum stress, proteasomal dysfunction and cell death
induce neurodegeneration is poorly understood at present
that can be partially rescued by malin. These findings
and the possible mechanism of dysfunction of protein
suggest that the neuronatin-induced aberrant Ca2+
degradation pathways in LD is also not clear. Since malin
signaling and endoplasmic reticulum stress might underlie
is an E3 ubiquitin ligase and its mutation causes to LD, it
LD pathogenesis.
National Brain Research Centre
Publications
I. J. Sharma, D. Mukherjee, S. N. Rao, S. Iyengar, S. K.
Shankar, P. Satishchandra and N. R. Jana (2013).
Neuronatin mediated aberrant calcium signaling and
endoplasmic reticulum stress underlie neuropathology
in Lafora disease. Journal of Biological Chemistry,
288, 9482-9490.
Presentations
1. N. R. Jana. Understanding the physiological function
of malin and pathogenesis of Lafora disease. Annual
Meeting of Society for Biological Chemists (SBCI),
Kolkata, 2012.
2. D. Mukherjee, J. Sharma, S.N Rao, S. K. Shankar, P.
Satishchandra and N. R. Jana. Neuronatin mediated
altered calcium signalling and ER stress cause
neuropathology in Lafora disease. Annual Meeting of
Society for Biological Chemists (SBCI), Kolkata, 2012.
3. N. R. Jana, J. Sharma, D. Mukherjee, S. N. Rao, S. K.
Shankar and P. Satishchandra. Neuronatin mediated
aberrant calcium signaling underlie neuropathology
Figure 2. Immunohistochemical staining of neuronatin
in Lafora disease. Annual meeting of the Society for
and ubiquitin in control (15 years old) and two different LD
Neuroscience (SFN), New Orleans, 2012.
brain biopsy samples (LD1 and LD2 of 17 and 23 years old
respectively). Lower panel of neuronatin staining shows
higher magnification images. Arrow indicates neuronatin
1. Understanding the physiological function of malin,
or ubiquitin-positive inclusions. Arrowhead pointed the
a ubiquitin ligase mutated in Lafora's Progressive
cell or neurites exhibiting high level of neuronatin in LD
brain. PAS staining was conducted to confirm the presence
Myoclonus Epilepsy. Department of Biotechnology.
of Lafora bodies (indicated by arrow) in LD brain samples.
Govt. of India. Grant No: BT/PR13590/Med/30/286/2009
In negative control (NC), LD brain section was processed
dt. 17-09-2010.
without neuronatin antibody. Scale bars; 40 um in smaller
magnification images and 20 um in higher magnification
images. Bottom panel shows higher magnification images of
I. Drs. S. K. Shankar and P. Satishchandra, National Institute
localization of neuronatin or ubiquitin into Lafora bodies.
of Mental Health and Neurosciences, Bangalore.
National Brain Research Centre
Principal Investigator
Pankaj Seth
Research Fellows
Shaily Malik, Manju Tewari, Mahar Fatima
and Chitra Singal
Project Assistants
Aparna Pandey, Ankita Srivastava, Monika
Sharma and Rabia Khatoon
Technical Assistant
Durgalal Meena and Naushad Alam
Human Immunodeficiency Virus-1 (HIV-1) virus traffics
suggests that neuron-glial interactions are of paramount
and resides in human brain as latent infection for several
importance for optimal neuronal functions. Perturbations
years in HIV-1 patients. While advent of combinatorial
in neuron-glial interactions have been implicated in several
anti-retroviral therapy (cART) has successfully limited viral
neurodegenerative disorders such as Alzheimer's disease,
replication in circulating blood cells, it has failed to do so
Parkinson's disease and HIV-1 associated dementia.
in brain tissue of HIV/AIDS patients. The poor penetration
of cART drugs into central nervous system (CNS) is the
Our laboratory is investing efforts to decipher intricacies
leading cause of their inability in clearing the virus from
of the neuron-glia interactions using a human fetal brain
brain, making brain as "HIV-1 sanctuary". The HIV-1 in brain
derived cell culture system. We are currently investigating
reservoirs has potential to repopulate the host circulation.
whether HIV-1 Tat protein affects neuron-glia interactions,
Low viral load in circulating blood cells is reported following
and if it does, how? We are employing live cell imaging
successful cART in majority of AIDS patients. Interestingly
techniques to evaluate the role of HIV-1 Tat on alterations
even though cARTs have failed to clear the virus from brain,
of intracellular calcium in glial cells, particularly astrocytes,
a significant improvement in the neurocognitive functions
and its relation to neuron damage. Our data suggest that
has been reported. This is perhaps because continuous
HIV-1 Tat modulates intracellular calcium ion concentration
pouring of virus from blood into brain is prevented in
which is mediated via purinergic receptors on glial cells. We
patients undergoing cART. Although prevalence of frank
observed that HIV-1 Tat resulted in a significant increase
dementia in HIV/AIDS patients has decreased following
in mRNA and protein levels of a particular purinergic
cART, a milder form of HIV-1 associated neurocognitive
receptor on primary cultures of human astrocytes.
disorder (HAND) is prevalent in around 50% of HIV/AIDS
Ongoing experiments are suggestive of the fact that
patients undergoing cART as HIV-1 and HIV-1 transactivator
HIV-1 Tat mediated neuronal damage is indeed mediated
of transcription (Tat) protein continues to affect normal
by astrocytes, as agonists and antagonists of purinergic
brain functions. This suggests that neurocognitive deficits
receptors directly influence neuronal damage as assayed
would continue to be cause of morbidity in HIV/AIDS
by apoptotic assays in our settings. We have confirmed the
patients until eradication of virus occurs from the host.
functionality of the over-expressed purinergic receptors
Efforts to design novel approaches to address this problem
using live cell imaging tools and time lapse microscopy.
of morbidity in HIV/AIDS patients is mandatory to reduce
We performed calcium imaging studies by employing
the burden of compromised cognition in AIDS survivors.
non ratiometric fluorescent dyes and high resolution
time lapse microscopy. Calcium imaging studies indicate
Cognitive abilities and optimal neuronal functions are
robust increase in intracellular calcium levels in human
supported by astrocytes in several ways. Astrocytes
astrocyte cultures following exposure to HIV-1 Tat protein
being the most abundant type of brain cells contribute
(Figure-1). Further, we observed that HIV-1 Tat treatments
significantly to normal brain physiology. Recent literature
to neuron-glia coculture resulted in significant decrease
National Brain Research Centre
in the expression of glutamate receptors on astrocytes.
disorders in HIV/AIDS and drug abusing patients.
Interestingly, we also observed a subsequent increase
of glutamate concentrations in supernatant of these
In addition to this, we continue to pursue our quest into
co-cultures that account for the increase in neuronal
HIV-1 and drug abuse co-morbidity with our experiments
death following exposure to HIV-1 Tat protein. Further
focused to investigate effect of opiates and HIV-1 Tat on
experiments to investigate astrocyte mediated neuronal
properties of human neural stem cells. We have convincing
damage are currently pursued in detail using a well
data to believe that HIV-1 Tat and morphine adversely
characterized human astrocyte-neuron co-culture system.
affect proliferation of human neural stem cells under
We have several interesting leads in this direction and
acute and chronic exposure of these agents. Importantly,
believe our findings will provide novel insights into role of
the co-morbidity of HIV-1 Tat and opiates does not affect
astrocytes in HIV-1 induced neuronal damage.
the viability of human neural stem cells. We utilized well
characterized human fetal brain derived neural stem cell
Clinical and basic science studies reveal augmented
model and observed that co-exposure of HIV-1 Tat and
neurological complications in drug abusing HIV/AIDS
opiate significantly reduced the number of Ki67 positive
patients due to enhanced neuronal damage. Literature in the
cells as well as exhibited reduced proliferation by other
area of neuroAIDS suggests that human neural stem cells are
proliferation assays. Detailed experiments were designed
susceptible to HIV-1 infection and harbor the virus for long
to dissect out cellular and molecular mechanisms that may
durations. Furthermore, several clinical and experimental
underlie this phenomenon. Our data from flow cytometry
studies have established the link between HIV-1 and
suggests that HIV-1 Tat and morphine stall human neural
opiate induced disturbances in their growth dynamics.
stem cells in the G1/S phase of cell cycle and fail to progress
The molecular mechanisms underlying the alterations in
into the S-phase. Furthermore mRNA and protein studies
neural stem cell properties with concurrent HIV-1 infection
reveal that Tat and morphine down-regulate Cyclin D1 and
and il icit drug use are poorly understood. Our laboratory
several cell cycle regulatory proteins affecting cell cycle
has recently contributed in this area and demonstrated
progression and proliferation of human neural stem cells. In
that the neurotoxic protein HIV-1 Tat alters the proliferative
addition to this, HIV-1 Tat and morphine attenuated SOX-2
ability of human fetal brain derived neural stem cel s. We
transcription factor that culminates into directly affecting
demonstrated enhanced neurotoxicity due to comorbidity
proliferation of human neural stem cells. These findings
of HIV-1 Tat and opiates in human neurons. These findings
have far reaching clinical implications in understanding
provide scientific basis for poor prognosis of neurological
comorbidity of drugs of abuse and HIV/AIDS.
Figure: HIV-1 Tat increases in intracellular calcium levels in human neuron-glia coculture. Human neuron-glia co-cultures
were treated with vehicle or HIV-1 Tat protein at 100 ng/ml concentration and calcium imaging was performed using non-
ratiometric dye fluo-3 as calcium indicator. Fluorescence imaging of intracellular Ca2+ was performed with epifluorescence
imaging system (NIKON eclipse) upon exciting cells at 488nm with laser. Images were acquired with a CCD camera from random
fields containing 80-100 cells. Initially basal level of fluorescence was recorded and then cells were treated with HIV-1 protein
Tat (100 ng/ml). The change in fluorescence intensity of Fluo-3 was used as a measure of increased intracellular calcium and
depicted in the figure. Notice a robust increase in the calcium concentration following HIV-1 Tat treatment as most cells fluoresce
due to activation of calcium indicator fluo-3. Scale represents intensity of Calcium fluorescence.
National Brain Research Centre
9. Pankaj Seth, Manju Tewari, Ankita Srivastava (Invited
1. Pankaj Seth (Invited Speaker): Neural Stem Cells - a Tool
Lecture and Chairperson): Glia Mediated Neuronal
for Basic Research. At Amity University, Haryana, India,
Injury in HIV-1 Neuropathogenesis: "the other side of
April, 2012.
the coin" At 27th Annual Meeting of Society of
2. Pankaj Seth, Pretty Garg and Manju Pant Tewari. Role
Neurochemistry, All India Institute of Medical Sciences,
of Neuron Glia Crosstalk in HIV-1 Neuropathogenesis.
India, February, 2013.
11th International Symposium on Neurovirology and
Presentations by Students –
2012 Conference on HIV in the Nervous System. New
York, USA, May, 2012.
10. Shaily Malik, Rinki Saha and Pankaj Seth. "Modulation
3. Pankaj Seth (Invited Seminar in Calendar of Events
of human neural precursor cell proliferation and
of National Institutes of Health (NIH)): Neuron - Glia
differentiation by HIV-1 transactivating protein, Tat and
interactions during HIV Neuropathogenesis. National
drugs of abuse". 18th Annual Scientific Conference of
Institutes of Health (NIH), Bethesda, USA, May, 2012.
Society on Neuroimmune Pharmacology, Hawaii, USA.
4. Pankaj Seth (Invited Session Speaker): Neural Stem
Cells - a window into neurodegenerative diseases. At
11. Manju Tewari. Role of Glial cells in HIV-1 neuropatho-
Rajiv Gandhi Institute of Technology, Amethi, During
genesis. At NeuroCon 2013 meeting at Indian Institute
National Seminar on "Stem Cell an emerging Healthcare
of Chemical Biology, Kolkata, India, January 2013.
Frontier" during August, 2012.
5. Pankaj Seth (Invited Session Speaker and Co-Chair):
HIV-1 Induced Neuronal damage: Who is to be
This work is supported by NBRC Core, DBT, Indo-US R21
blamed? At XXX Annual meeting of Indian academy of
ICMR and NIH-RO1 funds.
neurosciences, Guru Nanak Dev University, Amritsar,
India, Oct, 2012.
6. Pankaj Seth (Guest Speaker): Neural Stem Cells – an in
vitro model to understand brain disorders. At Seminar
1. S. Sharma, NBRC, India.
Series on Stem Cell Application in health care at Amity
2. N. Thapar and A. Singh, Civil Hospital, Gurgaon, India.
University, Haryana, India October, 2012.
3. U. Ranga, JNCSAR, Bangalore, India.
7. Pankaj Seth (Invited Resource Person): Are we doing
4. Pardo, Johns Hopkins University, Baltimore, USA.
enough to cure HIV/AIDS in India? Seminar on HIV/
5. A. Nath, National Institute of Health, Bethesda, USA.
AIDS and Drug Abuse, Ukrul District, Manipur, India,
6. S. Buch, University of Nebraska Medical College,
Nebraska, USA.
8. Pankaj Seth, Shaily Malik and Rinki Saha (Invited
Speaker and Co-Chairperson): In vitro neural stem
cell system - An opportunity to "peep" inside the
Shaily Malik Integrated-PhD student in Laboratory - IBRO
degenerating human brain? At NeuroCon 2013 meeting
International Travel Grant (January-June 2012) for presenting
at Indian Institute of Chemical Biology, Kolkata, India,
her work at Society of Neuroimmune Pharmacology (SNIP),
Hawaii, USA, April 2012.
National Brain Research Centre
Principal Investigator
Ellora Sen
REGULATED ABERRANT
Research Fellows
Deobrat Dixit, Sadashib Ghosh, Ruchi
Ghildiyal, Piyushi Gupta, Fahim Ahmad
Post Doctoral Fellow
Dr. Sanchari Sinha, Dr. Arpita Chatterjee
Project Assistant
SIGNALING CASCADES
Nikhil P Anto, Ashwat Nagarajan
Technical Assistant
Shanker Dutt Joshi
Lab Attendant
Rajesh Kumar Kumawat
Glioblastoma multiformes (GBM) represents one of the
TLR4. Inhibition of HMGB1 inhibited TLR4 and vice versa
most malignant brain tumors characterized by intense
suggesting the existence of HMGB1-TLR4 axis in glioma cells.
proliferation and poor prognosis. Gliomas are also
Interestingly, HMGB1 inhibition prevented IL-1β induced
characterized by their effective immune escape mechanisms
HLA-G expression. Human β-defensin-3 (hBD-3) - primarily
that evade immuno-surveillance. As inflammation is
associated with adaptive and innate immune responses, is
an indispensable participant in tumor progression, the
elevated in GBM tumors. Importantly, hBD3 prevented IL-
focus of our group is to understand the importance of
1β induced HLA-G, TLR4, HMGB1 expression and release of
inflammatory mediators in the transcriptional regulation of
pro-inflammatory mediators. Our studies indicate that hBD3
genes associated with evasion of immune response, survival
abrogates IL-1β induced HLA-G expression by negatively
and resistance to apoptosis in GBM. The highly resistant
affecting key molecules associated with its regulation.
nature of GBM to chemotherapy has also prompted us
to identify new treatment strategies that target aberrant
signaling pathways. Dissecting the role of inflammation
in the regulation of aberrant signalling and transcriptional
circuitries associated with glioma progression is an active
area of research in the lab.
Understanding regulation of genes associated with
immune evasion
β-defensin-3 negatively regulates TLR4-HMGB1 axis
mediated HLA-G expression in IL-1β treated glioma cells.
The non-classical HLA class-I antigen HLA-G contributes to
immune escape mechanisms in GBM. As we have previously
shown that IL-1β-HIF-1a axis connects inflammatory
and oncogenic pathways in GBM, we investigated the
role of IL-1β induced inflammation in regulating HLA-G
expression. IL-1β increased HLA-G and Toll like receptor
4 (TLR4) expression in a HIF-1a dependent manner.
Inhibition of TLR4 signaling abrogated IL-1β induced
Figure 1. Proposed model indicating hBD3 mediated
HLA-G. IL-1β increased the expression of HMGB1- a late
regulation of HLA-G through a TLR4-HMGB1 axis in IL-1
mediator of systemic inflammation, and its interaction with
National Brain Research Centre
2. Understand mechanisms that confer resistance to
canonical pathways including NFB. Although Shh inhibitor
apoptosis in GBM and identify new treatment strategies
SANT1 alone failed to induce cell death, it sensitized
that can manipulate the aberrant signaling pathways
glioma cells to Ras/NFB inhibitor Guggulsterone via
to induce death.
Caspase 9 activation. While SANT1 decreased Gli1 activity,
Guggulsterone inhibited Ras and NFB activity. Functional
(i) Targeting JNK-NFB axis sensitizes glioma cells to TNF
inactivation of Ras/NF
induced apoptosis
B axis sensitized glioma cells
to SANT1. Guggulsterone induced ERK contributed to
As we have previously reported that certain anti-cancer
Caspase-9 activation. SANT-1 reduced proliferation of
chemotherapeutics can sensitize glioma cells to TNF
glioma stem-like spheres. Since SANT-1 and Guggulsterone
induced apoptosis by abrogating NFB activation, we
differentially targets stem-like and non-stem glioma cells
investigated the potential of Oncrasin in sensitizing glioma
respectively, this combination warrants investigation as an
cells to TNF induced apoptosis. Oncrasin reduced glioma
effective anti-glioma therapy.
cell viability, inhibited TNF mediated NFB activation,
and sensitized cells to TNF induced apoptosis. Oncrasin
increased JNK phosphorylation and pharmacological
inhibition of JNK rescued Oncrasin-induced apoptosis. JNK
inhibition prevented Oncrasin induced decrease in TNF
induced NFB activity, and inhibition of NFB increased JNK
phosphorylation in TNF treated cells. Oncrasin inhibited
anchorage independent growth of glioma cells in a JNK
dependent manner. By elucidating the existence of JNK-
NFB cross-talk that regulates resistance to TNF induced
apoptosis, this study has highlighted the importance of
JNK in regulating viability of glioma cells.
Figure 3. Proposed model demonstrating Guggulsterone
mediated sensitization of the glioma cells to Gli-1 inhibitor
induced apoptosis.
Publications
1. Dixit D, Ghildiyal R, Anto NP, Ghosh S, Sharma V and Sen
E (2013). Guggulsterone sensitizes glioblastoma cells
to Sonic hedgehog inhibitor SANT-1 induced apoptosis
in a Ras /NFB dependent manner. Cancer Letters.
2. Gupta P, Ghosh S, Nagarajan A, Mehta VS, Sen E (2013).
β-defensin-3 negatively regulates TLR4-HMGB1 axis
mediated HLA-G expression in IL-1β treated glioma
cells. Cellular Signaling. 7;25(3):682-689.
3. Gupta P, Dixit D and Sen E (2013).Oncrasin targets the
JNK-NFB axis to sensitize glioma cells to TNF induced
apoptosis. Carcinogenesis 34(2): 388-396.
Figure 2. Schematic depicting Oncrasin mediated
4. Ghildiyal R, Dixit D, Sen E. (2012). EGFR inhibitor BIBU
sensitization of glioma cells to TNF induced apoptosis
induces apoptosis and defective autophagy in glioma
through regulation of JNK-NFB axis.
cells. Molecular Carcinogenesis.
5. Tewari R, Choudhury SR, Mehta VS, Sen E. (2012) TNF
regulates the localization of CD40 in lipid rafts of glioma
(ii) Inhibition of Ras /NFB axis sensitizes glioblastoma cells to
cells. Mol Biol Rep.;39 (9):8695-9.
Shh inhibitor induced apoptosis.
Shh pathway effector Gli1 is overexpressed in gliomas
and is induced by both canonical Shh signaling and non-
6. Granted European patent: European Pat. 2.367 784 B1–
National Brain Research Centre
"Bicyclic triterpenoid Iripallidal as a novel anti-glioma
New Delhi, November 2012.
and anti-neoplastic therapy in vitro". Patent granted
7. Piyushi Gupta. β-defensin-3 negatively regulates TLR4-
on 02.01.2013, International publication number (WO
HMGB1 axis mediated HLA-G expression in IL-1 treated
glioma cells. Carcinogenesis, New Delhi, November
8. Sadashib Ghosh and Ellora Sen. TNF induced HIF-
1- catenin axis regulates MHC class I gene activation.
I. Ellora Sen. Inflammation mediated oxidative stress in
Carcinogenesis, New Delhi, November 2012.
cancer. 4th International Congress on Cell Membrane
9. Ghildiyal R. Inhibition of EGF Receptor by BIBU induces
and Oxidative Stress, Suleyman Demirel University,
apoptosis and defective autophagy in glioma cells.
Isparta, Turkey. June 2012. Invited lecture and Session
Carcinogenesis, New Delhi, November 2012.
10. Deobrat Dixit. Inhibition of Ras /NFB axis sensitizes
glioblastoma cells to Shh inhibitor induced apoptosis.
Indian Academy of Neuroscience, Amristsar, October
1. Ellora Sen. HLA gene regulation in glioma: Role of
Inflammation. Indian Association of Cancer Research,
11. Ellora Sen. Hypoxia-Inflammation nexus: A potential
New Delhi, February, 2013.
anti-glioma target? Indian Society of Neuro-Oncology
2. Deobrat Dixit. Guggulsterone sensitizes glioblastoma
(ISNOCON), NIMHANS, Bangalore, April, 2012.
cells to Sonic hedgehog inhibitor SANT-1 induced
apoptosis.Emerging Trends and Challenges in Basic and
Translational Research in Biochemistry, Department of
1. Understanding signaling circuitries involved in
Zoology, Banaras Hindu University, Varanasi, Feruary
transcriptional regulation of genes associated with
survival and immune response in an inflammatory
3. Ellora Sen. TNF regulates resistance to apoptosis
environment: Implications in glioblastoma progression.
in glioblastomas. 3rd International Cancer Research
Funded by Department of Biotechnology, Govt. of India.
Symposium, Kolkata, December 2012.
4. Ellora Sen. Inflammation and resistance to apoptosis in
gliomas: The rehabilitation of thoughts. Carcinogenesis,
New Delhi, November 2012.
Dr. VS Mehta, Paras Hospital
5. Deobrat Dixit. Inhibition of G9a in glioma cells inhibits
hypoxia signalling and induces cell death through
apoptosis and autophagy. Carcinogenesis, New Delhi,
1. Shakuntala Amir Chand Award, 2009, Indian Council of
November 2012.
Medical Research (ICMR), awarded 2013
6. Fahim Ahmad. Identification of signalling circuitries
2. Elected member of Guha Research Conference
regulating telomerase activity in glioma. Carcinogenesis,
National Brain Research Centre
MOLECULAR CHANGES
Principal Investigator
Shiv K Sharma
RELEVANT TO SYNAPTIC
Research Fellows
Chinmoyee Maharana, Shilpa Mishra,
Kaushik Sharma, Kiran Pandey, Kautuk
Kamboj, Apurva Agrawal
Project Assistants
Bandhan Mukherjee, Neha Sharma,
Rashmi Ray
Lab Attendant
Activity-dependent molecular and synaptic changes are
observations make KCl a good stimulus to study molecular
known to play crucial roles in memory formation. However,
processes relevant for synaptic plasticity and memory.
the detailed processes involved in these changes are not
Calcium influx through NMDA receptors is critical for
clearly understood. We are examining activity-dependent
the development of LTP. We found that stimulation of
molecular changes with a focus on the underlying signaling
NMDA receptors also results in enhanced alpha tubulin
acetylation. We extended this study and examined the
molecular mechanisms that regulate activity-dependent
alpha tubulin acetylation in the hippocampus. Our results
Activity-Dependent Alpha Tubulin Acetylation
show that blocking the activity of a serine/threonine kinase
In our previous study, we showed that treatment of
using pharmacological inhibitors blocks KCl-induced alpha
hippocampal slices with KCl increases alpha tubulin
tubulin acetylation, suggesting a critical role of a kinase in
acetylation. KCl treatment of neuronal cells produces
the regulation of this molecular event. Further, we found
molecular changes that are important for plasticity and
that the kinase activity is also required for the NMDA
memory formation. More importantly, KCl induces long-
receptor-mediated increase in alpha tubulin acetylation.
term potentiation (LTP), which is considered a cellular
Thus, a particular kinase is critical for activity-dependent
mechanism of memory formation. These and related
acetylation of alpha tubulin in the hippocampus.
Figure KCl increases surface glutamate receptor levels. Primary hippocampal neurons
were untreated (control) or treated with KCl (KCl). Surface glutamate receptors were
labeled with specific antibody and detected using secondary antibody linked to a dye.
National Brain Research Centre
Since the level of acetylation of a protein is controlled by
downstream of cAMP that help in sustained ERK activation.
the relative activities of acetylase and deacetylase enzymes,
We find that blocking the translational and transcriptional
we next asked whether activity-mimicking stimulus
events differentially affect cAMP-induced immediate and
regulates deacetylase activity. We found that KCl treatment
sustained ERK activation. Given the significance of cAMP
reduces the activity of a deacetylase in the hippocampus.
signaling pathway in LTP and memory formation, our results
Furthermore, KCl-induced reduction in deacetylase activity
indicate that cAMP-induced sustained ERK activation may
requires the activity of the particular serine/threonine
play important roles in these processes.
kinase. Collectively, these results show that KCl activates
a kinase, which in turn inhibits the activity of a specific
deacetylase leading to increased acetylation of alpha
tubulin in the hippocampus.
1. Maharana C, Sharma KP, Sharma SK (2013) Feedback
mechanism in depolarization-induced sustained
It is well known that glutamate receptors play crucial roles
activation of extracellular signal-regulated kinase in the
in LTP and memory. We are examining the mechanisms
hippocampus. Sci Rep. 3:1103.
involved in glutamate receptor trafficking. Our results
suggest that KCl enhances glutamate receptor expression
on the membrane surface (Fig 1). We are now examining the
1 S.K. Sharma and C. Maharana. Mechanisms of pattern-
processes involved in enhanced expression of glutamate
dependent activation of extracellular signal-regulated
receptors on the membrane.
kinase in the hippocampus. Society for Neuroscience
meeting, Oct. 13-17, 2012, New Orleans, USA.
Mechanisms of cAMP-Induced Activation of Extracellular
2 Kiran Pandey and Shiv K. Sharma. HDAC inhibition
Signal Regulated Kinase
facilitates surface recruitment of AMPA receptors in the
In our previous study, we showed that KCl treatment
hippocampus. XXX Annual Meeting of Indian Academy
of hippocampal slices induces sustained activation
of Neurosciences, 27-30 October, 2012, Guru Nanak
of extracellular signal-regulated kinase (ERK). We also
Dev University, Amritsar.
investigated the mechanisms involved in keeping ERK
activated long after the stimulus has been withdrawn.
We are now examining whether other agents having
This work is supported by NBRC Core.
important roles in synaptic plasticity and memory induce
sustained ERK activation. Our results show that increasing
the cAMP level induces sustained ERK activation in the
Degree awarded (Ph.D.)
hippocampal slices. We are examining the mechanisms
Chinmoyee Maharana
National Brain Research Centre
MOLECULAR APPROACHES
Principal Investigator
TO UNDERSTAND THE
Research Fellow
Deepak Kumar Kaushik, Arshed Nazmi, Iqbal
Mohamed Ariff, Sourish Ghosh
Research Associate
AND PHARMACOLOGY
Dr Nabonita Sengupta, Dr Menka Chanu
OF INFECTION AND
Project Assistant
Dwaipayan Adhya, Kiran Kundu, Sriparna
Mukherjee
Technical Assistant
DISORDERS OF CENTRAL
Kanhaiya Lal Kumawat
Lab Attendant
Immune responses in the central nervous system (CNS) are
Our research question evolves around the understanding
very common, despite its perception as a site of immune
the molecular basis of host-pathogen interaction in viral
privilege. These responses can be mediated by resident
infection of the brain and the signaling events associated
microglia (brain macrophages), which are innate immune
with neuro-inflammation. In last few years our research
cells without direct counterparts in the periphery. While
have been primarily focused on neuropathology of host
peripheral immune access to the CNS is restricted and
pathogen interaction in Japanese encephalitis Virus (JEV),
tightly regulated, the CNS is capable of dynamic immune
causative agent of most common Viral encephalitis in Asia-
responses to a variety of insults. Infections, trauma,
pacific region. The impact of emerging and reemerging viral
stroke, toxins and other stimuli are capable of producing
induced encephalitis is being felt globally. In India, although
an immediate and short lived activation of the innate
many encephalitis outbreaks have been associated with
immune system within the CNS. This acute neuroimmune
JEV several outbreaks have remained undiagnosed. The
or neuroinflammatory response includes activation of the
association of Chandipura virus with the recent outbreak
resident immune cells (microglia) resulting in a phagocytic
of acute encephalitis in Andhra Pradesh implicates that
phenotype and the release of inflammatory mediators
this virus should be considered as an emerging pathogen
such as cytokines, chemokines, and other inflammatory
of substantial public health importance. As a new initiative
mediators. The sustained release of inflammatory mediators
we have started a project to understand the host-pathogen
works to perpetuate the inflammatory cycle, activating
interaction in Chandipura Virus infection.
additional microglia, promoting their proliferation, and
resulting in further release of inflammatory factors,
Japanese encephalitis virus (JEV) predominantly infects
and help in recruiting leukocytes from the periphery.
neurons and causes damage to the central nervous system
Neurodegenerative CNS disorders, including multiple
(CNS). Neural stem/progenitor cells (NSPCs) constitute
sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease
multi-potent stem cell population in postnatal/adult brain,
(PD), Huntington's disease (HD), amyotrophic lateral sclerosis
with capacity to differentiate into neurons, astrocytes or
(ALS), tauopathies, and age-related macular degeneration
oligodendrocytes. NSPCs are known to play a pivotal role
(ARMD), are associated with chronic neuroinflammation
in CNS repair mechanisms during various neurological
and elevated levels of several cytokines. The recognition of
disorders. Previous studies from our laboratory have
microglia as the brain's intrinsic immune system, and the
shown that JEV infection of NSPCs depletes the stem-
understanding that chronic activation of this system leads
cell pool, which may result in impaired repair functions
to pathologic sequelae, has led to the modern concept of
leading to motor and cognitive deficits in survivors. In the
present study, we evaluated the effect of JEV infection on
National Brain Research Centre
differentiation potential of NSPCs isolated from BALB/c
mouse pups (Post natal day 7). Results clearly indicated that,
JEV infection was more robust in undifferentiated NSPCs
as compared to differentiated ones. Further, JEV infected
NSPCs showed hampered differentiation and arrested
migration in adherent neurosphere cultures. Interestingly,
the neuronal differentiation appeared to be more severely
affected by JEV as compared to astrocyte differentiation.
The transcription factors involved in both neuronal and
astrocyte differentiations were significantly decreased
upon JEV infection. Overall, results presented in this study
comprehensively provide first evidence for JEV induced
alteration of neuronal and astrocyte differentiation (Figure
Figure 2 Effect of JEV infection on expression of β-III tubulin
and nestin in undifferentiated (Day 0) and, differentiated
(day 3) neurosphere. Undifferentiated and differentiated
neurospheres were stained for newly generated neuronal
marker β-III tubulin (FITC, green) and NSPC marker nestin
(Alexa 594, red).
enhanced immune suppression creating an anti-viral milieu.
Expression of pro-inflammatory cytokines and chemokines
is suppressed along with increased expression of anti-
inflammatory molecules. Histone deacetylases (HDACs)
have known inflammatory properties. The significance
of the HDACs can be assumed from the predictome
map (Figure 3) that shows the possible protein-protein
Figure 1 Effect of JEV infection on expression of GFAP and
interactions between the four HDACs that are currently
nestin in undifferentiated (Day 0) and, differentiated (day
under investigation with other proteins, both in humans
3) neurosphere. Undifferentiated (Day 0) and differentiated
and in mouse, the model of our investigation. This map
neurospheres (day 3) were stained for astrocyte marker GFAP
has been based on a database of predicted functional
(FITC, green) and NSPC marker nestin (Alexa 594, red) along
associations among proteins in many different organisms
with DAPI (blue).
with the help of the VisANT Project, a web-based data
exploration tool. We have shown, through modulation of
HDACs JEV seems to play a crucial anti-inflammatory and
JEV is a common cause of encephalitis in humans.
anti-viral role in host macrophages. HDAC3 expression is
But, humans are dead-end hosts producing negligible
down-regulated on JEV-infection of macrophages which
viremia. The virus reaches the brain and causes massive
also corresponds with the inhibition of NFκB activity. This
inflammation. We have tried to understand the virus-host
clearly demonstrates that in macrophages, JEV promotes
interaction using the murine monocyte/macrophage cells,
a negative regulation of inflammatory responses through
an antigen presenting cell involved in eliciting an innate
the inhibition of HDACs.
immune response. We have found several interesting
phenomena occurring in JEV-infected macrophage
Besides studying fundamental aspects of JE neuropathology
cells which diverge from established observations. JEV
we are always keen to do translational research to develop
remains inside macropahges and appears to have little
newer generation of therapy for JE. Recently in collaboration
negative effect on viability. Expression studies of major
with Dr Guruprasad R. Medigeshi from Vaccine and
histocompatibility complexes (MHC) and co-stimulatory
Infectious Diseases Research Centre, Translational Health
molecules show inhibition of antigen presentation. There is
Science Technology Institute (THSTI), Gurgaon we have
National Brain Research Centre
showed that Bispidine-Amino Acid conjugates act as a
Mumbai based pharmaceutical company is manufacturing
novel scaffold for the design of antivirals that block JEV
the PFOS (Powder for oral Solution) formulation of the
replication. We have demonstrated that the amino-acid
Minocycline and placebo for this trial. NBRC has been
conjugates of 3,7 diazabicyclo[3.3.1]nonane can serve as
appointed CliniRx, a CRO to monitor the trial. As of today's
a molecular scaffold for development of potent antivirals
date out of 332 adults screened 97 has been enrolled
against encephalitic viruses. Our findings will provide a
and 577 children screened 177 has been enrolled for this
novel platform to develop effective inhibitors of JEV and
trial. Simultaneously follow up study is going on with the
perhaps other RNA viruses causing encephalitis.
patients who have left the hospital after the administration
of drug or placebo.
Based upon our previous findings a Phase III clinical trial
in JE patients has started at Department of Pediatrics, CSM
Alongside with biology of JE, our laboratory is also deeply
Medical University (King George Medical College), Lucknow.
engaged in basic research to understand the transcriptional
Prof. Rashmi Kumar, Head of the Department of Pediatrics
regulation of microglial activation. Microglia are the
is supervising this trial. This trail has been registered to
resident macrophages of the Central Nervous System
Clinical Trial Registry of India. Unimark Remedies Ltd a
(CNS), which secrete several pro- and anti-inflammatory
cyto-chemokines in response to pathogenic stimuli. One
key player that is believed to drive this neuroinflammatory
process is interleukin (IL)-1β, a pro-inflammatory cytokine
that is up-regulated in Alzheimer's disease (AD), Parkinson's
disease, multiple sclerosis, and other neurodegenerative
disorders. Once secreted, IL-1β binds to IL-1 receptor
present on microglia and initiates the production of
inflammatory cytokines in microglia. However, the detailed
information regarding the molecular mechanisms of IL-1
triggered inflammatory pathways in microglia is lacking.
We have focused our study on the role of Krüppel-like factor
4 (Klf4) in mediating the regulation of pro-inflammatory
gene expression upon IL-1β stimulation in microglia. We
have demonstrated that stimulation of microglia with
IL-1β robustly induces Klf4 via PI3K/Akt pathway which
positively regulates the production of endogenous IL-1β as
well as other pro-inflammatory markers, cyclooxygenase-2
(Cox-2), monocyte chemoattractant protein-1 (MCP-1)
and interleukin-6 (IL-6). In addition, we have reported that
Klf4 negatively regulates the expression of iNOS, thereby
playing a key role in regulating the immunomodulatory
activities of microglia. Our findings strongly suggest that
Klf4 is one of the key players of inflammation and therefore
is one of the key targets of therapeutic intervention in
neurodegenerative diseases which has distinct pathology
of inflammation.
Publications
1. I M Ariff, M C Thounajam, S Das, and A Basu (2013)
Japanese Encephalitis virus infection alters both
Figure 3 A predictome of interactions between HDAC1,
neuronal and astrocytic differentiation of Neural Stem/
2, 3 and 4 with other proteins, both in human and in mice.
progenitor Cells. J Neuroimmuno Pharmacology (in
Given the complex and varied array of proteins with which
these HDACs can interact, a multitude of pathways and
2. V Haridas, K S Rajgokul, S Sadanandan, T Agrawal,
processes could be affected by the suppression of these
V Sharvani, M V S Gopalkrishna, M B Bijesh, K L
Kumawat, A Basu, G R Medigeshi (2013) Bispidine-
National Brain Research Centre
amino acid conjugates act as a novel scaffold for the
inflammation: a new therapeutic target? BioWorld 2012,
design of antivirals that block Japanese encephalitis
Kusuma School of Biological Sciences, Indian Institute
virus replication. PLoS Neglected Tropical Diseases
of Technology Delhi, New Delhi, 10th-12th December,
2012. (Invited speaker)
3. A Majhi, A Mahanti, K Kundu, K Dutta, A Basu, and
6) D K Kaushik, M C Thounajam, and A Basu (2012) Kruppel
B Bishayi (2013) Increased resistance of immobilized-
Like Factor 4 regulates microglial activation in response
stressed mice to infection: correlation with
to Interleukin-1. XXX Annual Meeting of Indian
behavioral alterations. Brain, Behaviour, and
Academy of Neurosciences, 27th-30th October, 2012,
7) A Nazmi, I A Mohammed, K Dutta, K Kundu, and A Basu
(2012) Neural Stem/Progenitor Cells induces conversion
1. M C Thounajam, D K Kaushik, and A Basu (2013)
of encephalitogenic T-cells into CD4+-CD25+- FOXP3+
MicroRNAs in the Brain: It's regulatory role in
Regulatory T-cells. XXX Annual Meeting of Indian
Neuroinflammation.
Molecular
Academy of Neurosciences, 27th-30th October, 2012,
2. D K Kaushik, and A Basu (2013) A friend in need
8) A Nazmi, K Dutta, K Kundu, and A Basu (2012) TLR7
may not be a friend indeed: role of microglia in
regulates expression of suppressor of cytokine
neurodegenerative diseases. CNS & Neurological
signaling (SOCS) in CNS post Japanese Encephalitis
Disorders-Drug Targets (in press)
Virus infection. XXX Annual Meeting of Indian Academy
3. N Sengupta, and A Basu (2013) Japanese Encephalitis
of Neurosciences, 27th-30th October, 2012, Amritsar
Virus Infection: Effect on brain development and repair.
9) A Basu (2012) Basic and Translational Studies at the
Current Science (in press).
Host-Pathogen Interface. UGC refresher courses for
Book Chapter
college and university faculty members, Center for Biotechnology, JNU, 20th July, 2012
K Dutta, A. Nazmi and A Basu (2013) Japanese encephalitis virus and human CNS infection. In Neuroviral Infections, ed
10) A Basu (2012) Therapeutic targeting of Krüppel like
S.K. Singh, D. Ruzek, CRC Pr 1 LLc. [ISBN-10: 1439868522]
factor 4 abrogates inflammation and oxidative stress in brain. 4th International Congress on Cell Membrane
and Oxidative stress. 26th-29th June. Suleyman Demirel University, Isparta, Turkey. (Invited speaker)
1) A Basu (2013) The transcriptional regulation of
microglial function: the tightrope walk of CNS innate
11) A Basu (2012) Antiviral and Neuroprotective Role of
immune response. Society for Neurochemistry Meeting
Octaguanidinium Dendrimer-Conjugated Morpholino
2013, AIIMS, New Delhi, 21-23rd February. (Invited
Oligomers in Japanese Encephalitis. 9th International
Symposium on Polymer Therapeutics: From Laboratory to clinical practice 28th -30th May, 2012, Valencia, Spain.
2) A Basu (2013) Host pathogen interaction in Japanese
(Invited speaker)
Encephalitis Virus infection: from bench to bedside. South Asian University, New Delhi, 8th February, 2013.
(Invited speaker)
of Suppressors of cytokine signaling (SOCS) in
Psychoneuroimmunology Preconference workshop
the pathogenesis of Japanese Encephalitis [Funded
(Neurocon 2013), IPGMER, Kolkata, 17th January, 2013.
by Department of Biotechnology (awarded along
(Invited speaker)
with the National Bio Science Award for Career Development)]
4) A Basu (2013) Neuronal Innate Immune Response in
Japanese Encephalitis Virus infection. 3rd Molecular
2) To study the role of Neuronal innate immune response
Virology Forum meeting, National Institute of Virology,
in Japanese encephalitis virus infection [Funded by
Pune, 10-11th January 2013. (Invited speaker)
5) A Basu (2012) Krüppel Like Factor 4 in neuro-
3) To elucidate the role of inflammasome and other
National Brain Research Centre
molecular events leading to Hypoxia induced neuro
inflammation [Funded by Life science Research Board,
F1000 Faculty Member of the Year Award' for the Faculty of
DRDO (No LSRB-213/EPB/2010)]
*The awards recognize Faculty Members who have made
"Innate Immune responses in flaviviruses" with Dr
the most significant contribution to the F1000 service over
Guruprasad Medighesi, VIDRC, THSTI, Gurgaon.
the past year, as judged by their editorial team.
National Brain Research Centre
Principal Investigator
Ranjit Kumar Giri
CULTURES ARE USEFUL
Research Fellow
Pankaj S. Ghate
Technical Assistant
ALZHEIMER'S DISEASE
Rajiv Kumar Mishra
Lab. Attendant
Alzheimer's disease (AD) is a progressive and irreversible
beta amyloid production and to study its effect on major
neurodegenerative disease of elderly people. It is the most
cell types of an adult brain, my lab is working towards
common cause of dementia worldwide. Genetic linkage
developing an alternative in vitro model employing CNS
studies of early onset familial Alzheimer's disease (FAD)
stem cells. Since, beta amyloid peptide is the central and
had identified amyloid precursor protein (APP), Presenilin 1
key molecule in the development of AD, endogenous
(PSEN1) and Presenilin 2 (PSEN2) as three causative genes.
production and multimerization of human beta amyloid
Mutations in these genes increase the production and
peptides are warranted in developing AD model in vitro.
aggregation of more fibrillogenic beta amyloid peptides,
the hallmark pathology of Alzheimer's disease. Very little
My lab has developed 4 separate neurosphere lines. Two
is known about the role of beta amyloid peptides toward
of these were positive for huAPPswe and huPS1ΔE9 gene
neurotoxicity. In order to study the mechanisms in AD
(Tg +ve) and two are negative (Tg –ve) which served as
associated neurodegeneration in humans, transgenic
wild type controls. Our results demonstrated that, Tg +ve
animals expressing human FAD genes were developed.
lines express huAPPswe and huPS1ΔE9 transgenes at
Though these transgenic mice show beta amyloid deposits,
mRNA level (by RT-PCR) which are not present in Tg -ve
astrogliosis, impaired learning abilities and mild cognitive
neurosphere lines.
impairments, the role of beta amyloid peptides towards
neurotoxicity remained puzzled. Moreover, the effect
Western blot analysis of neurosphere lysates and
of beta amyloid on various mature brain cells is also not
immunofluorocytochemistry (IFCC) analysis indicated the
known. Therefore, an alternative model that retains the
expression of human APP protein and its fragments only
capacity to generate major cell types of adult brain and
in Tg +ve neurosphere lines but not in transgenic negative
generates human beta amyloid peptides endogenously is
lines. Presence of beta amyloid peptides in neurosphere
lysates was minimal in transgenic positive neurosphere
lysates. However, western blot analysis of human beta
Earlier reports have demonstrated the presence of neural
amyloid peptides from culture supernatants of both
stem cells in adult and embryonic brain of animals and
Tg –ve and Tg +ve neurosphere cultures demonstrated
humans. These CNS stem cells can differentiate towards
the presence of human beta amyloid peptides in all Tg
major cell types of an adult brain except microglia in vitro
+ve neurosphere lines but not at all in Tg -ve lines. These
and in vivo. It is not clear why these cells fail to replenish the
beta amyloid peptides are seen both as monomers and
neuronal cell loss seen in AD, especially in hippocampus
oligomers. Moreover, resolution of beta amyloid peptides
where CNS stem cells are enriched. Thus, we hypothesize
in Tris-Bicine Urea gel followed by western blot analysis
that beta amyloid peptides might be affecting the normal
clearly demonstrated the presence of human beta amyloid
functioning of CNS stem cells. So, to recapitulate most
40 and beta amyloid 42 peptides in Tg +ve (NS1 and NS3)
of the pathological features of AD, such as, endogenous
but not in Tg -ve NS lines. Furthermore, beta amyloid 42 to
National Brain Research Centre
beta amyloid 40 ratio is higher in the present model than
and accumulation of human beta amyloid peptides in Tg
any other in vitro model of AD.
+ve neurosphere cultures in parallel with transgenic mice
brain. Collectively, it indicates the genesis of a newer in
Intracellular beta amyloid load is another pathological
vitro model for AD that has the potential to address other
feature of various cells in AD brain. Immunofluorescent
pathological effect of beta amyloid peptides on various
staining of adherent cells from neurosphere cultures
adult brain cells like neurons, astrocytes, oligodendrocytes
demonstrated Tg +ve neurosphere lines have significant
and CNS stem cells.
increased immunosignal towards 6E10 antibody than
Tg -ve neurosphere lines without epitope retrieval. Upon
epitope retrieval, Tg +ve cells showed significant increased
immunosignal over non-epitope retrieval counterparts,
1. Ranjit K. Giri. Utilization of Neurosphere Culture in the
whereas Tg -ve cells showed little increased signal than
Development of a Novel in vitro model of Alzheimer's
non-epitope retrieval cells. Increased immunosignal in
Disease, McLaughlin Research Institute, Great Falls,
Tg+ve neurosphere cultures might be due to the presence
Montana, USA, 2012.
of beta amyloid peptides in beta-sheet isoforms or in
oligomeric form that required epitope retrieval prior to
its interaction with 6E10 antibody. Taken together, the
This work is supported by Ramalingaswami Fel owship from
results strongly indicate the expression, protein misfolding
DBT (102/IFD/SAN/758/2007-08) and NBRC core fund to PI.
National Brain Research Centre
CURCUMIN INDUCES
Principal Investigator
Ranjit Kumar Giri
APOPTOSIS THROUGH
Research Fellow
INTRINSIC APOPTOTIC
Himakshi Sidhar
Lab Attendant
NEUROBLASTOMA CELLS
Neuroblastoma is the tumor of sympathetic nervous
CDKs, etc. However, very little is known about the effect
system. It develops from uncommitted neural crest
of curcumin on neuroblastoma cells. To understand the
cells. It accounts for 8-10% of childhood cancers. These
molecular mechanisms underlying curcumin mediated
tumors can either spontaneously regress in stage I and
neuro 2a cell death, we first established cytotoxicity of
II or exhibit resistance to current cancer therapy in stage
curcumin on neuro 2a cells. Our results from LIVE-DEAD,
III and IV patients. In addition, side effects of current
MTT assay demonstrated the toxic effect of curcumin on
chemotherapy or radiotherapy are major area of concern.
neuro 2a cells (Figure 1). DNA fragmentation and TUNEL
Therefore, alternative and safer therapy for neuroblastoma
positive cells were significantly higher in curcumin treated
is warranted.
neuro 2a cells which suggest the possible activation of
apoptotic pathways (Figure 2). Our results also showed
Dietary phytochemicals with anti-cancer properties might
increased activation of caspase-9 and caspase-3 in curcumin
serve as a superior alternative. These small molecules are
treated neuro 2a cells. However, caspase-8, a molecular
non-toxic and might have an enduring effect on human
marker for the activation of extrinsic apoptotic pathways
health. Curcumin is the main active component of a
was not activated in curcumin treated neuro 2a cells (data
common Indian spice, turmeric (Curcuma longa). Turmeric
not shown). Thus, curcumin kills neuro 2a neuroblastoma
is used as traditional medicine in Indian ayurveda because
cells by employing intrinsic apoptotic pathway.
of its anti-oxidant and anti-inflammatory properties.
Moreover, curcumin preferably induces apoptosis in highly
List of genes related to apoptosis are growing. Expression
proliferating cancer cells but not in normal cells. Cytotoxic
of some of these genes is associated with sensitizing the
effect of curcumin has been addressed on various cancer
cancer cells to currently used cancer drugs. Curcumin may
cell lines including cervical, ovarian cancers etc. Curcumin
activate those genes as well. To study these, our future
mediates apoptosis through both caspase-dependent and
-independent pathways. Literature survey strongly suggests
that curcumin has a wide range of molecular targets and
1) The effect of curcumin on the induction of newer pro-
activates/upregulates pro-apoptotic genes like p53, JNK,
apoptotic genes in neuro 2a cells.
Akt, Rb and many more. It also downregulates oncogenes
2) The molecular mechanism underlying curcumin-
and anti-apoptotic genes like c-Myc, Ras, MAPKs, PI3K,
mediated induction of these genes in neuro 2a cells.
National Brain Research Centre
Figure 01 Curcumin activates cell death in mouse neuro
Figure 02 Curcumin-mediated cell death is
2a neuroblastoma cells. Neuro 2a cells were treated with
associated with apoptotic pathways. Neuro 2a cells
10, 25, 50 µM curcumin or with equal amount of DMSO
were treated with 10, 25, 50 µM curcumin or with equal
(control) for 24 hrs. A) LIVE DEAD assays were performed.
amount of DMSO (control) for 24 hrs. A) Agarose gel
Fluorescent images were captured from three random
electrophoresis of genomic DNA isolated from control
fields employing similar image acquisition settings. Live
and curcumin treated neuro 2a cells were performed.
(green) and dead (red) cells were counted. Results strongly
Results indicate, curcumin induces genomic DNA
indicate that, curcumin causes neuro 2a cell death in a dose
fragmentation in a dose dependent manner. B) TUNEL
dependent manner. B) MTT assays on curcumin treated
assays were also performed in curcumin treated or
neuro 2a cells were performed. Amount of formazan was
untreated cells. DAPI (blue) and TUNEL labeled (green)
measured by absorbance at 560 nm with a reference
cells were imaged from three random fields with same
wavelength at 620 nm. Our results indicate the curcumin-
image acquisition settings. The increase in number
mediated neuro 2a cell death is dose dependent. Data
of TUNEL positive cells in curcumin treated cells than
represents mean ± standard deviation of at least three
corresponding controls indicate that curcumin induces
independent experiments (*p<0.001).
cell death by activating apoptotic pathways.
Funding
This work is funded by NBRC Core and partially by Ramalingaswami fellowship (w2/IFD/SAN/758/2007-08) and a grant from
DBT (No BT/PR10721/Med/30/ 105/2008) to PI.
National Brain Research Centre
NON-CODING RNA –
Principal Investigator
Sourav Banerjee
MEDIATED REGULATORY
Research Fellows
MECHANISMS INVOLVED
Pushpa Kumari, Mandrita Barua
Project Assistant
IN DEVELOPMENT AND
Sarbani Samaddar, Prajwal Thakre
Technical Assistant
FUNCTION OF NEURONAL
D. Narendar, Musadiq Hussain
All brain functions ranging from simple reflexes to complex
activity dependent control of synapse formation. To assess
behaviors are regulated by vast neuronal network. The
the differential expression of lincRNAs upon synaptic
communication gateway of neuronal connectivity, known
activation, neurons from mouse brain in primary culture
as synapse, is established during development and in adult
was stimulated by membrane depolarization and then the
brain with spatio-temporal precision. Synapses are dynamic
expression pattern of these non-coding transcripts were
and modification of synaptic connections (or synaptic
assessed by quantitative real time PCR method. To our
plasticity) occurs in an experience dependent manner.
surprise, we observed that two novel lincRNAs have been
Thus, identifying the processes that regulate synaptic
differentially expressed in response to neuronal activation.
development and function will be essential to understand
This poses some interesting questions: Are these lincRNAs
how synapses are formed and how they modulate function
critical for synapse formation? If so, what type of synapse
of neuronal networks.
(excitatory or inhibitory) development is modulated by
these lincRNAs? What are the molecular mechanisms of
Among various regulators that modulate neuronal
activity dependent synapse development –mediated by
development and plasticity, much interest is currently
lincRNAs? Which synaptogenic tarnscripts are regulated by
focused on post-transcriptional control by non-coding
these lincRNAs? Is the regulatiory control of synaptogenic
RNAs. Of particular interest is long non-coding RNAs or
programme by lincRNAs occurring in a calcium responsive
linc RNAs (>200 nucleotide long transcript that does not
manner? We are currently using wide range of biochemical,
encode proteins) that were initially thought to be spurious
cell biological and biophysical approaches to address these
transcriptional noise. However, emerging reports suggest
that expressions of such lincRNAs are spatio-temporally
regulated during development and also in adult animal.
Apart from lincRNAs, we are investigating the role of micoRNA
LincRNAs are expressed ubiquitously and also exihibit cell
(miRNAs), 21-23 nucleotide long non-coding transcripts,
type specific expression pattern in various neuroanatomical
in modulation of synaptic function. miRNAs regulate gene
region. More recently, lincRNAs have emerged as a
expression reversibly by binding to the 3' untranslated
key gene regulatory switch that can modulate gene
region (UTR) of target mRNAs resulting in translational
expression system through various transcriptional, post-
repression or transcript degradation. Importantly, spatio-
transcriptional and translational controls. Taken together,
temporal regulation of dendritic protein synthesis has
these observations raise the possibility that lincRNAs may
emerged as a key modulator of synaptic plasticity. Thus, the
be involved in development of precise neuronal circuitry.
reversibility of miRNA-mediated regulation of their targets
makes them perfect candidates for activity-dependent
To address the role of lincRNAs in development and
control of synaptic plasticity. Emerging reports have shown
function of neuronal connectivity, we are screening a list
that miRNAs guide a multi-protein complex, known as the
of lincRNAs; those that are differentially regulated during
RNA-induced silencing complex (RISC), to specific sites on
National Brain Research Centre
mRNAs targeted for gene silencing. Interestingly, a miRNA
Binding Proteins (RBPs) that can remodel ribonucleoprotein
can target multiple mRNAs and also a single mRNA can be
complex. RBPs can bind to target mRNAs through specific
regulated by multiple miRNAs at the synapse. This poses
cis-element located in non-coding region of the transcript.
some intriguing questions: How is specific miRNA-target
Among several neuronally expressed RBPs, Cytoplasmic
interaction at the synapse is modulated in response to
Polyadenylation Element Binding protein (CPEB) has already
neuronal activity? How does miRNA-mediated transcript-
been implicated in the synaptic plasticity mechanism.
specific control of protein synthesis modulate synaptic
CPEB binds to the Cytoplasmic Polyadenylational Element
(CPE) and modulates dendritic translation of specific
sets of dendritic mRNAs, such as -CaMKII and tPA and
To elucidate novel biochemical mechanisms that are
thereby modulates synaptic plasticity. Interestingly, our
critical for miRNA-mediated control of synaptic function,
observations also revealed that the 3' untraslated region
our laboratory is focusing on two important aspects: (1)
(3'UTRs) of -CaMKII and tPA mRNAs are targeted by a
Molecular mechanisms underlying the transcript specificity
dendritically enriched miRNA and that binding sites for this
of miRNA-mediated control of protein synthesis at the
miRNA and for CPEB are juxtaposed at the 3'UTR of both
synapse. (2) Significance of transcript-specific translational
mRNAs. Based on these observations, we hypothesized that
control in fine-tuning of synaptic plasticity. Towards these
CPEB can bind to set of dendritic RNAs through CPE element
key questions, a recent study identified a set of RNA
and can modulate RISC dependent translation from these
mRNAs. We are performing genome wide screen to identify
mRNAs those that are translationally regulated through
CPEB –mediated control of RISC function. Furthermore,
we will explore the mechanistic details of this novel
mechanism of synaptic plasticity. Future directions will be
to assess the implications of these novel mechanisms in
modulation of emerging behavior, such as anxiety, feeding
Presentation
1. Sourav Banerjee: Tune it up: Modulation of neuronal
circuitry and synaptic mechanisms of plasticity. IISER
Pune. August 2012.
Synaptic localization of a RNA binding protein
Ramalingaswami Fellowship, DBT.
National Brain Research Centre
Principal Investigator
Dr. Sayali C. Ranade
Environmental factors acting early in life either organize or
Next we showed that maternal iron deficiency during the
permanently alter the developing physiological systems
period of gestation and lactation affects hippocampal
resulting in ‘prenatal programming'. Nutrition represents
development in F1 pups. The hippocampus dependant
one of the major important variables directly affecting
spatial memory function checked in radial arm maze
growth and development of the organism. The effects
is specifically affected by maternal iron deficiency. We
of malnutrition or undernutrition on brain development
also showed association of these memory defects with
have been demonstrated over the past 40 years in humans
components of stress pathway. This is the first report
and in experimental animal models. Different types
suggesting involvement of stress pathway in iron deficiency
of malnutrition affect maturation of the brain and the
induced spatial memory dysfunction.
development of cognitive function, resulting in behavioural
abnormalities and disturbances in learning and memory.
Our future goal is to define the optimum nutritional
Since cerebellum and hippocampus are the brain structures
conditions for perinatal development. These issues are of
central to learning and memory circuits, we decided to
great social importance and impact. The outcome of such
focus on studying the effect of maternal malnutrition on
studies will help us design and develop new preventive
brain development with special attention to hippocampus
strategies and intervention therapies.
and cerebellum. Three different types of malnutrition
paradigms used are caloric restriction, inadequate amount
of protein in the diet and condition of low iron content.
1. Ranade Sayali, Nawaz S, Pavan Kumar R, Rose AJ,
Our first major achievement this year is to show effect of
Gressens P and Mani S (2012). Early protein malnutrition
protein malnourishment on cerebellar development and
disrupts cerebellar development and impairs motor co-
motor co-ordination. We showed that protein energy
ordination. Br J Nutr. 107(8) :1167-75.
malnutrition suffered by the mother during the period of
2. Ranade Sayali, Nawaz S, Chakrabarti A, Gressens P
gestation and lactation has an adverse effect on cerebellar
and Mani S (2013). Spatial memory deficits in maternal
neurogenesis in F1 pups leading to the altered number
iron deficiency paradigms are associated with altered
of neurons and glia in cerebellum. Early life protein
glucocorticoid levels. Hormones and behaviour.
malnutrition also leads to delays of motor development.
National Brain Research Centre
Figure 2: Effect of different paradigms of maternal iron
deficiency on glucocorticoid receptor expression in DG
and CA1 of hippocampus. The images showing effect
of different paradigms of maternal iron deficiency
on levels of glucocorticoid receptors checked in
immunohistochemistry using GR M20 antibody. panels
(A),(E) panels (B),(F) panels (C),(G) and panel(D),(H)
are representative images of CA1 regions at different
magnification in control, pre-ID, post-ID and pre+post-
ID respectively. Significant reduction of staining was
seen in pre+post-ID in panels (D), ( H) and post-ID
groups (panels C and G). Panels (I),(M) panels (J),(N)
panels (K),(O) panels (L),(P) are representative images
of DG region of hippocampus at different level of
magnification of control, pre-ID, post-ID and pre+post-
Figure 1: Maternal protein deficiency reduces number
ID respectively. Note the complete disappearance of
of calbindin positive Purkinje cells: Figure four shows
GR-M20 staining in panels (L) and (P) representing
number of calbindin positive cells in the Purkinje layer of
group pre+post-ID. Scale bar is 100 m.
cerebellar folds (A) The x-axis shows age and y axis shows
mean number of calbindin positive cells per m Purkinje
layer. The panel B, C, D shows the calbindin positive
cells at different developmental stages in both control
and protein deficient groups. A significant reduction is
The Iron deficiency work is supported by WOS-A,
seen in no. of calbindin positive cells in Purkinje layer of
Department of Science and technology.
protein deficient mice at all three developmental stages
(N=5 for both the groups at all ages). Bars are mean
The protein malnutrition work is supported by CIFPRA,
+SEM. Scale bar is 100 m.
Indo-French grant and ICMR.
National Brain Research Centre
Systems & Cognitive
Prof. Neeraj Jain
Dr. Soumya Iyengar
Dr. Narender K. Dhingra
Dr. Yoganarasimha Doreswamy
Principal Investigator
OF SOMATOSENSORY
Post Doctoral Fellows
Prem Chand, Arkadeb Dutta (Until November 2012)
AND MOTOR SYSTEMS
Research Fellows
Leslee Lazar, Niranjan Kambi, Radhika Rajan,
Hisham Mohammed, Vasav Arora, Manika Arora,
Priyabrata Halder, John Thomas (Joined September
2012), Atanu Datta (Joined September 2012)
Project Assistants
G Naga Rajesh, Anshu Khandelwal
Technical Assistant
Mithlesh Singh
Laboratory Assistant
Organization of Somatosensory and Motor Systems
Mechanisms of large-scale brain reorganization.
and the Effects of Spinal Cord Injuries
Brain reorganization following spinal cord injury occurs
Following injuries to dorsal columns of the spinal cord at
at multiple sites in the brain, which include area 3b,
cervical levels, topographically organized sensory inputs in
areas S2/PV and ventroposterior nucleus of the thalamus.
the somatosensory cortex undergo changes such that face
Since the shift in topographic boundaries is beyond
inputs expand and reactivate neurons in the deafferented
any known existing normal connections, it is generally
hand region. Research work in our laboratory is focused
accepted that the changes must involve neuronal growth
towards understanding the extent, nature and mechanisms
(Jain et al., PNAS 2000). It has been variously proposed
of such changes in the somatosensory and motor systems. We
that the growth could be (i) corticocortical, (ii) subcortical,
use a combination of neurophysiological, neuroanatomical
occurring in the brain stem nuclei, or (iii) taking place at
and behavioural techniques in our laboratory. We perform
multiple sites. However, it is not known if in monkeys with
unilateral lesions of dorsal columns leaving spinothalamic
chronic spinal cord injuries there is an expansion of the face
and other ascending and descending pathways intact.
representation into the cuneate nucleus, which normally
Behavioural effects of these lesions are restricted to an
receives inputs from the hand.
inability to form a precision grip. Our previous work at
NBRC has shown that lesions of the dorsal columns in
In order to answer this question we mapped area 3b
adult macaque monkeys lead to large-scale reorganization
and the brain stem nuclei of monkeys with long-
in the second somatosensory areas S2 and PV. As in area
term lesions of the dorsal columns at cervical levels.
3b, chin inputs expand into the deafferented hand region
The results show that as expected, chin inputs had
(Tandon et al., Journal of Neuroscience, 2009). This was
expanded into the deafferented hand region of area 3b
rather unexpected because areas S2/PV continue to receive
(Fig. 1). Furthermore, recordings from neurons in the
normal intact hand inputs via spinothalamic pathways after
brain stem nuclei showed that neurons in the cuneate
dorsal column lesions. Subsequently we showed that loss of
nucleus responded to touch on the chin showing that
sensory inputs also results in subtle but significant changes
brain reorganization takes place even at the earliest stages
in movement representation in the primary motor cortex
of the information-processing stream. Since the lesion in
(Kambi et al., Journal of Neuroscience, 2011). Major focus
the case illustrated here did not completely deafferent the
of research during the last year has been on determining
cuneate fasciculus, at some recording sites responses to
mechanisms of large-scale brain reorganization. The work
touch on the hand were present in both area 3b and the
done during the year is described below.
cuneate nucleus.
National Brain Research Centre
Figure 1. Reorganization of the area 3b and cuneate nucleus in a monkey with lesion of the dorsal columns of the spinal cord.
(A) Details of the somatotopy showing expansion of the chin inputs (pink) into the hand region. The somatotopy is shown on
the posterior bank of the central sulcus. Blue arrowhead marks location of the normal hand-face border. Chin representation
to the right of the arrowhead is in the normal face area. (B) Two cross sections from the medulla showing a series of electrode
penetration through the trigeminal and the cuneate nuclei. Note that neurons in the cuneate nucleus respond to touch on the
chin (pink). Since the lesion was partial, neurons at few recording sites also respond to touch on the hand.
Figure 2. A schematic showing normal dorsal column-
medial lemniscus somatosensory pathway and the current
state of knowledge of brain reorganization. (A) Inputs from
the skin enter the spinal cord and ascend in the dorsal
columns to the brain stem nuclei. Inputs from the hand are
located in the cuneate nucleus and those from the face in
the trigeminal nucleus. Second order neurons project from
cuneate nucleus to the ventroposterior (VP) nucleus of the
thalamus. In the VP nucleus inputs from the hand and face
terminate in its lateral (VPL) and medial (VPM) subdivisions
respectively. Third order neurons primarily project to area
3b, the primary somatosensory area in the post-central
gyrus. Further projections go to other somatosensory
areas including those in the lateral sulcus (S2 and PV).
(B) Following chronic lesions of the dorsal columns of
the spinal cord at cervical levels in adult animals, chin
inputs expand into the deafferented hand region in all the
somatosensory regions examined – the cuneate nucleus,
VPL, area 3b and areas S2 and PV.
National Brain Research Centre
Figure 3. (A) Somatotopic map of area 3b showing expansion of chin inputs medially into the deafferented hand region
in a monkey with lesion of the dorsal columns. Blue arrowhead marks location of the normal hand-face border. (B) A
peristimulus time histogram and raster plot showing neuronal responses to a periodic 1 Hz stimulus of the chin at the
recording site marked by a circle. This recording site is located in the reorganized part of area 3b. (C) Neuronal responses
at the same site after normal chin representation in the cortex were inactivated by injecting lidocaine via a capillary tube.
There was no effect on the cortical responses.
During the year we also investigated if corticocortical
mechanisms contribute to large-scale brain plasticity. In
1. Arkadeb Dutta, Niranjan Kambi, Partha Raghunathan,
monkeys with chronic lesions of the dorsal columns, we
Subhash Khushu, Neeraj Jain (2013). Large-scale
first mapped area 3b to establish that chin representation
reorganization of the somatosensory cortex of adult
had expanded into the deafferented hand region. We then
macaque monkeys revealed by fMRI. Brain Structure
inactivated the normal chin region of area 3b using short
and Function. (In Press).
acting sodium channel blocker lidocaine. For continuous
inactivation by lidocaine we used a custom-built capillary
2. Shashank Tandon, Niranjan Kambi, Hisham Mohammed
injection system, which can simultaneously record neuronal
and Neeraj Jain (2013). Complete reorganization of the
activity. The system was designed to allow independent
motor cortex of adult rats following long-term spinal
movement of the electrodes attached to the capillary tube.
cord injuries. European Journal of Neuroscience. (In
Our results showed that responses to tactile stimulation of
the chin were not affected in the deafferented hand region
by inactivation of the normal chin area. The expanded
chin representation remained intact. Thus normal chin
Department of Information Technology.
inputs are not essential for the observed expansion of the
Department of Biotechnology.
chin representation in the cortex. Therefore, large-scale
brain reorganization is not mediated by corticocortical
mechanisms. Further experiments are underway to
determine mechanisms of plasticity.
Prof P Raghunathan, NBRC; Dr S Khushu, INMAS
National Brain Research Centre
Principal Investigator
Soumya Iyengar
Research Fellow
Shankhamala Sen
Technicians
Arvind Singh Pundir, Krishan Sharma
Lab Assistant
The main aspects of cognition include attention, learning
neurons could be seen within MSt on both sides and
and memory, language and perception as well as motor
appeared to correspond to the songbird Area X. We also
responses. A number of behavioural studies have
found an oval nucleus on either side of the midline in
demonstrated that amongst birds, corvids (including
the posterior part of the arcopallium which appeared to
crows, rooks, jays and starlings) can perform at par with
be homologous to the songbird RA (a premotor cortical
non-human primates on cognitive tasks which require
region, nucleus robustus arcopallium).
causal reasoning, imagination, flexibility and foresight.
Recently, studies on the organization of neural circuits,
We have used immunohistochemical staining to
gene expression and neurotransmitters in the avian brain
demonstrate that as in other birds and mammals, the
have demonstrated that the caudal nidopallium (NC) is the
cytoplasm and elaborate dendrites of large cells in the
avian homologue of the prefrontal cortex, which is known
VTA-SNc were highly positive for the enzyme tyrosine
to be important for cognition in mammals. However,
hydroxylase which is important for the breakdown of the
there are almost no studies available on brain structure or
neurotransmitter dopamine. The size of TH-positive cells in
function in general or of the NC in particular of corvids.
the VTA-SNc complex varied from small to large in a rostro-
caudal gradient. Medium and small sized TH-positive
We were interested in studying the brain structure of
neurons were also present in the septum (except for the
indigenous species of corvids (house crows, Corvus
medial septal nucleus, which contained a number of TH-
splendens, and jungle crows, Corvus macrorhynchos)
positive fibers) and occasionally in the arcopallium near
and comparing them with other species of birds such as
RA. All parts of the striatum (including MSt, LSt and Area X)
zebra finches (songbirds), as a first step to understanding
contained a dense plexus of fibers highly immunoreactive
why crows are adept at performing complex cognitive
for TH, such that the striatum could be clearly distinguished
tasks. Preliminary experiments from our lab show
from the pallium. Within the pallium, the nidopallium had
that the basic brain architecture of house crows was
the lowest density of TH-positive fibers, followed by a slight
similar to that in Japanese jungle crows (Izawa and
increase in the density of these fibers in the mesopallium.
Watanabe, 2007). Different divisions of the pallium or
The overlying hyperpallium contained the highest density
avian cortex (hyper-pallium, mesopallium, nidopallium
of TH-positive fibers in the rostral part of the corvid brain.
and entopallium) could be discerned from each other
The NC also contained a high density of TH-positive fibers
based on cytoarchitecture and the location of various fiber
although it cannot be clearly demarcated from other pallial
tracts revealed by Nissl staining. Different components of
regions based on staining for TH. Since TH is a marker
the corvid basal ganglia were similar in structure to that
for dopaminergic input and there is a higher density of
of songbirds and could be divided into the lateral and
TH-positive fibers in NC and the hyperpallium, our data
medial striatum (LSt and MSt) and globus pallidus (GP).
suggests that these regions may be important for the
Interestingly, an oval area containing densely packed
remarkable cognitive abilities of corvids.
National Brain Research Centre
Figure 1: A coronal section of the crow brain (upper panel,
right) demonstrating the presence of tyrosine hydroxylase
(TH) in the meso- (M) and nidopallium (N) which are
avian homologues of the cortex (pallium). This image
also demonstrates high levels of TH immunoreactivity in
the avian striatum (MSt, Medial striatum). A Nissl-stained
coronal section is shown on the left for comparison. TH is
used as a marker for the neurotransmitter dopamine which
is known to be involved in cognition. High-power images
(lower panel) demonstrate the presence of TH-positive
neurons in the substantia nigra (SNC) and TH-positive
fibers (arrows) in the hyperpallium (H), another subdivision
of the pallium.
System" awarded in 2010 and NBRC Core funds.
This study is supported by a grant from DST (SR/CSI/03/2010)
"Neurobiology and Understanding the Circadian System
Linkage of Cognitive Performance in an Avian Model
Prof. Vinod Kumar, Delhi University, Delhi.
National Brain Research Centre
OPIOID MODULATION
Principal Investigator
Soumya Iyengar
Research Fellows
Sandeep Kumar, Uzma Din,
Project Assistant
Sudha Sharma
Technicians
Arvind Singh Pundir, Krishan Sharma
Lab Assistant
Zebra finches are an excellent model system to study
LMAN (red) is called the anterior forebrain pathway and is
vocalization. Adult male zebra finches sing highly
important for song learning during development. Area X
stereotyped or fixed songs in adulthood in two different
and the VTA-SNc (ventral tegmental area – substantia nigra
contexts: to court females (female-directed song) or in
complex) are important for context-dependent singing in
isolation (undirected song). Further, zebra finches possess
adult zebra finches. Area X projects to the VTA-SNc (ventral
well-characterized neural circuits (the song control system
tegmental complex) via the VP (ventral pallidum). The VTA-
or SCS, Fig. 2) which underlie song learning, vocalization
SNc region releases high levels of the neurotransmitter
and auditory perception, as in humans. The SCS is
dopamine (DA) into Area X when adult male birds sing to
homologous to the basal ganglia pathway in mammals.
females (Modified from Gale et al., 2008).
The neural circuit connecting the song control nuclei HVC
and RA (robust nucleus of the arcopallium) is important for
We had earlier demonstrated that the endogenous
vocalization. HVC also projects to Area X (a nucleus of the
opioid system modulates different kinds of behavior,
avian basal ganglia) which projects to DLM (dorsolateral
including vocalization in adult male zebra finches. Systemic
nucleus of the thalamus) which in turn projects to LMAN
injections of low doses of naloxone led to a decrease
(lateral magnocellular nucleus of the anterior nidopallium,
in both female-directed and undirected songs in adult
avian pallium or cortex). LMAN projects to both Area X and
male zebra finches, whereas other behaviours were not
RA, forming loops within the SCS. Area X further projects
affected. We also found changes in spectral features
to a region called the ventral pallidum (VP) which projects
of song (decrease in goodness of pitch, frequency and
to the ventral tegmental area – substantia nigra complex
amplitude modulation) and temporal features of song
(VTA-SNc). Earlier studies have shown that there is an
(increase in the duration of intersyllable intervals, Khurshid
increase in dopamine release by the VTA-SNc into Area X
et al., 2010a). These results suggested that naloxone
whenever male zebra finches sing to females. Further, it has
administration led to a decrease in the motivation to sing,
also been shown that LMAN and Area X are also involved in
since μ-ORs were present in the VTA-SNc (ventral tegmental
area - subtantia nigra complex) and other areas important
for motivation and reward. Changes in the spectral and
motor neurons in nXIIts (the hypoglossal nucleus,
temporal features of song probably resulted from blocking
tracheosyringeal part) which innervates muscles of the
μ-ORs expressed in song control areas of the brain which
syrinx or the vocal organ. HVC also projects to Area X
are important for vocalization (HVC and RA, robust nucleus
(a nucleus of the avian basal ganglia) which projects
of the arcopallium). In order to determine the site of action
to a thalamic nucleus DLM (dorsolateral nucleus of the
of naloxone in the brain which led to the changes in song
thalamus), which in turn projects to the cortical region
behaviour, we decided to inject naloxone specifically into
LMAN (lateral magnocellular nucleus of the anterior
different brain regions and then study changes in the
nidopallium). The circuit connecting Area X, DLM and
behaviour of adult male birds.
National Brain Research Centre
infusion in LMAN, although there was no change in this
measure when naloxone was injected into Area X. Further,
we implanted a cannula unilaterally into an area called the
ventral pallidum (VP) which receives projections from Area
X and in turn, projects to the VTA-SNc complex in one bird.
Infusions of naloxone in VP led to a decrease in the number
of songs that the bird sang to a female, compared to control
(vehicle) injections in this region. Our results suggest that
blocking μ-ORs in Area X, LMAN or VP during directed
song may affect the motivation to sing. It is possible that
blocking μ-ORs in these brain regions leads to changes in
the release of dopamine from VTA-SNc neurons which are
further downstream in this pathway, which is known to
be important for the production of directed song in adult
male zebra finches. Additionally, blocking opioid receptors
in LMAN also affects the quality of song, likely through its
Figure 2: The Song Control System of Adult Male Zebra
connections with the motor cortical region, RA.
finches. Auditory input from Field L (the avian homologue
of the auditory cortex) reaches HVC, the first of the song
control nuclei, which then projects to RA. The neural circuit
connecting HVC and RA (robust nucleus of the arcopallium;
1. Sharma J, Mukherjee D, Rao S, Iyengar S, Shankar
highlighted in blue) is important for vocalization. RA
SK, Satishchandra P and Jana NR (2013): Neuronatin
projects to motor neurons in nXIIts (the hypoglossal
mediated aberrant calcium signaling and endoplasmic
nucleus, tracheosyringeal part) which innervates muscles
reticulum stress underlie neuropathology in Lafora
of the syrinx or the vocal organ. HVC also projects to Area
disease. Journal of Biological Chemistry, 288(13);
X (a nucleus of the avian basal ganglia) which projects
to a thalamic nucleus DLM (dorsolateral nucleus of the
thalamus), which in turn projects to the cortical region
2. Iyengar S (2012): Development of the Human Auditory
LMAN (lateral magnocellular nucleus of the anterior
System. J. Indian Inst. Sci. 92:4; 427-440 (Invited review),
nidopallium). The circuit connecting Area X, DLM and
in the issue on "Development and Disorders of the
LMAN (red) is called the anterior forebrain pathway and is
Nervous System" edited by Dr. S. Mani.
important for song learning during development. Area X
and the VTA-SNc (ventral tegmental area – substantia nigra
complex) are important for context-dependent singing in
adult zebra finches. Area X projects to the VTA-SNc (ventral
1. Soumya Iyengar: Organization of the Vertebrate
tegmental complex) via the VP (ventral pallidum). The VTA-
Nervous System. Fourth DST-SERB school in Chrono-
SNc region releases high levels of the neurotransmitter
dopamine (DA) into Area X when adult male birds sing to
biology, North-Eastern Hill University (NEHU), Shillong,
females (Modified from Gale et al., 2008).
June 20, 2012.
2. Soumya Iyengar: Comparative Aspects of Brain
Evolution - Mammals versus Birds. Fourth DST-SERB
school in Chronobiology, North-Eastern Hill University
Cannulae were surgically implanted into Area X or LMAN
(NEHU), Shillong, June 21, 2012.
of adult male zebra finches unilaterally. After birds
recovered from surgery, a microdialysis probe was placed
3. Soumya Iyengar: Auditory System – I. Sixth DST-SERB
in the cannula and saline or artificial cerebrospinal fluid
School in Neuroscience, National Institute of Science
(the vehicle used to dissolve naloxone) or different doses
Education and Research (NISER), Bhubaneswar, Orissa,
of naloxone were infused into the brain while birds sang
December 18, 2012.
to females. Preliminary data demonstrated that injecting
4. Soumya Iyengar: Auditory System – II. Sixth DST-SERB
naloxone directly into Area X in awake singing birds led to
School in Neuroscience, National Institute of Science
an increase whereas injections into LMAN led to a decrease
Education and Research (NISER), Bhubaneswar, Orissa,
in the number of songs that birds sang to females compared
December 18, 2012.
to controls. We also found that there was a significant
5. Soumya Iyengar, Arvind Singh Pundir, Bishan
decrease in the mean pitch of songs sung during naloxone
Radotra, Praveen Kumar, PC Dikshit, SK Shankar, Anita
National Brain Research Centre
Mahadevan. Development of excitatory neural circuits
"Opioid Modulation of song in Male Zebra Finches" awarded
in the human auditory cortex. Poster presented at The
in 2010 and NBRC Core funds.
8th FENS Forum of Neuroscience, Barcelona, Spain, 14 -
18 July, 2012.
Prof. Neeraj Jain, NBRC.
This work is supported by a DST grant (SR/SO/AS-39/2009)
Niranjan Kambi (Prof. Jain's lab).
Vasav Arora (Prof. Jain's lab).
National Brain Research Centre
RETINAL CIRCUITRY:
Principal Investigator
Narender K. Dhingra
Research Fellows
Varsha Jain, Deepak Poria, Manvi Goel
Research Assistants
Sushma Dagar, Abhinaba Ghosh, Kaushik
Deka, Bhuvaneswari Ganesan
Technical Assistant
Sumit Mahapatra
Lab Attendant
Background & Significance
Retinal degenerative diseases such as Retinitis Pigmentosa
We have been studying retinal changes that follow
and Age-Related Macular Degeneration have high
photoreceptor degeneration. The primary objective of
incidence rates, and are among the leading causes of
this project is to understand the mechanism underlying
blindness. These diseases have varied etiology but are
oscillatory spike bursting observed in RGCs after
characterized by degeneration and loss of photoreceptors,
photoreceptor loss. We have found in two animal models
whereas inner retinal neurons, especially retinal ganglion
of retinal degeneration that synaptic activity in amacrine
cells (RGCs) are relatively preserved. Since RGCs, which
cells and bipolar cells is increased after photoreceptor loss.
transmit the retinal signal to the brain are preserved,
Currently we are quantifying GABA, glutamate and glycine
there is an immense interest in replacing the degenerated
receptors in inner retina after photoreceptor degeneration.
photoreceptors with a prosthetic device or stem cells.
We are testing the hypothesis that increased GABAergic
Retinal prosthesis is an electronic device surgically
signaling in amacrine cells results in increased feedback
implanted in eye to stimulate the retina through an array
inhibition of bipolar cell terminals, which eventually
of microelectrodes. The hope is that the device would
leads to oscillatory glutamate release in bipolar cells and
correctly encode the information in the visual scene,
thus oscillatory burst firing in RGCs. We are also testing
transmit it to the surviving RGCs, and thus produce artificial
the hypothesis that oscillatory activity originates in On
vision in blind patients. Similarly, the transplanted stem
bipolar cells and is passively transferred to Off pathway via
cells are expected to differentiate into photoreceptors
glycinergic pathway.
which would functionally integrate with the host neurons. Both these approaches have shown great promise in recent
Role of Brn3-expressing retinal ganglion cells in vision
years, but are yet to produce the desired clinical outcome.
Brn3 family of class IV POU-domain transcription factors,
Our working hypothesis is that the clinical success of these
including Brn3a, Brn3b and Brn3c play important roles
treatment approaches is linked to our understanding of
in differentiation, axonal pathfinding and dendritic
how the retinal circuitry develops and functions, normally
stratification of RGCs during development. The three Brn3
as well as in retinal degeneration. The overall goal of our
transcription factors are expressed in partially overlapping
research is to understand how retinal circuitry functions
subsets of RGCs in adult retina, raising the possibility that
normally, and how it responds to retinal degeneration.
they represent a combinatorial code. We showed previously
We believe that understanding normal retinal circuitry
that intrinsically-photosensitive RGCs (ipRGCs), which are
would also help design better treatment protocols for
thought to mediate non-image-forming visual functions,
retinal degeneration, and conversely, understanding
do not express Brn3a or Brn3c (Jain et al., 2012). However,
pathophysiology of retinal degeneration would also help
a specific subset of ipRGCs (non-M1 cells) express Brn3b.
unravel normal retinal function.
Based on these results and previous reports, we postulated
National Brain Research Centre
that Brn3 transcription factors are expressed exclusively by
reinforce the differentiation of the host Müller cells into
RGCs that mediate image-forming vision. Conversely, the
photoreceptors, with or without the growth factors.
M1 cells that do not express Brn3 transcription factors may
be involved exclusively in irradiance detection. We have
further probed these ideas by studying the expression
pattern of Brn3 after photoreceptor degeneration.
1. Goel M, Dhingra NK (2012) Müller glia express
The rationale is twofold: 1) The interplay between
rhodopsin in a mouse model of inherited retinal
photoreceptors and ipRGCs in mediating non-image-
degeneration. Neuroscience 225: 152-61.
forming visual functions, such as pupillary light reflex
(PLR) and circadian photoentrainment is not completely
clear, and 2) Although the Brn3b-positive and Brn3b-
1. S Dagar, NK Dhingra. Loss of photoreceptors in rd1
negative ipRGCs have been implicated in mediating PLR
mouse leads to selective upregulation of amacrine cell-
and photoentrainment respectively, it is not clear how
specific synaptic protein mRNAs. Annual Conference of
these specific cells or their function are affected in retinal
the Indian Academy of Neurosciences (Amritsar, India;
degeneration. We have found that a majority of M1 cells,
October, 2012).
which do not normally express Brn3b, start to express it in
the absence of photoreceptors in rd1 mouse. To confirm
2. V Jain, E Ravindran, R Guruswamy, NK Dhingra. Expression
that loss of photoreceptors leads to M1 cells expressing
of Melanopsin and its co-expression with Brn3b
Brn3b, we have looked at two additional animal models
alters in Mouse model of Retinal Degeneration FASEB
where photoreceptor degeneration is induced chemically.
summer research conference on Retinal Neurobiology
We have found interesting differences in PLR between the
and Visual Processing (Steamboat Springs, CO, USA; Jul-
two animal models, which we believe can be attributed to
changes in the Brn3b expression in ipRGCs.
3. NK Dhingra, A Ghosh. Loss of Photoreceptors in rd1
Mouse is Associated with Upregulation of GABAC
Role of Müller glial cells in rescue and recovery of
Receptors in Inner Retina. ARVO meeting (Fort
Lauderdale, USA; May, 2012).
We have been studying the potential role of Müller glial
cells in rescue and recovery of photoreceptors in retinal
degeneration. We showed previously that Müller cells in
rd1 mouse remain undifferentiated for several months and
This work is supported by Department of Biotechnology,
express rhodopsin, a mature rod photoreceptor marker,
Govt of India, and National Brain Research Centre.
but did not express other neuronal markers of retina. These
results suggested that Müller cells tended to differentiate
selectively into rods that are the primary targets of the PDE6
I. Dr. P Seth (NBRC): Use of Human Fetal Brain Derived
mutation in rd1 mouse (Goel and Dhingra, 2012). Currently,
Neural Precursor Cells in a Retinal Degeneration Model
we are carrying out a series of experiments to expand on
these results. For example, we are testing the hypothesis
II. Dr. M Ganguli (IGIB): To Study Efficiency of Cationic
that adding specific growth factors would reinforce the
Peptides to Deliver Plasmid DNA into Retinal Cells in
differentiation of Müller cells into photoreceptors. In
addition, we are growing pure Müller cells in culture and
III. Prof. SK Narayan (JNCASR): Using Photosensitive
transplanting them intravitreally into rd1 mouse to see if
Polymer Substrates to Stimulate Retinal Neurons after
they would differentiate into photoreceptors or would
National Brain Research Centre
Principal Investigator
Yoganarasimha Doreswamy
Research Fellows
UNDERLYING SPATIAL
Apoorv Sharma, Guncha Bhasin,
The hippocampus and related medial temporal lobe areas
also reflect encoding of behaviourally salient nonspatial
play a major role in learning and memory. The spatial
information onto the spatial framework provided by place
component of the memory is encoded in these brain
cells. Head direction cells present in various cortical and
areas as a cognitive map of the external environment,
subcortical areas, fire selectively when the animal's head
resulting in efficient spatial navigation, orientation and
is pointed in a particular direction in allocentric space
successful interpretation of external sensory cues. The
regardless of its location and serve as internal compass for
primary research focus of our laboratory is to understand
the animal. These are controlled by a complex interaction
how the brain constructs an internal representation of
between idiothetic cues and external landmarks. Strong
the outside world and how those representations are
coupling between head direction cells and place cells
stored and recalled as conscious memories, thus forming a
spatial relation between an organism and its environment.
Through in vivo neurophysiological studies in rodents, we
hope to understand the neural mechanisms underlying
spatial memory and navigation, which may lead to better
understanding of the memory deficits observed during
aging, brain injury and neurodegenerative diseases. Place
cells of the hippocampal formation and head direction
cell system plays a very critical role in spatial memory and
navigation, and acts as model system for deciphering the
neural network mechanisms by which the brain constructs
these cognitive representations from multimodal inputs.
Figure 1 Multitetrode electrophysiology data recording
The hippocampus is critically involved in learning and
set-up (A) and the behavioural recording room (B) for in
memory and has been suggested to play a major role in
vivo neurophysiological recordings.
episodic-memory, context-dependent learning, learning
of spatiotemporal sequences, which requires integration
of spatial and nonspatial representations. Spatially
have been reported, and the preferred firing locations/
active place cells selectively fires at specific location in
directions of place cells and head direction cells remain
an environment, indicating that the hippocampus may
strongly coupled to each other even when they become
form the locus of a "cognitive map" of the surrounding
completely uncoupled from external landmarks. The head
environment. Previous studies have shown that place
direction system is suggested to govern the orientation
cells are controlled by a complex interaction between self-
of the hippocampal spatial representation relative to the
motion cues and salient landmarks in the environment,
external environment. However, understanding the precise
and it has been suggested that the place cell firing may
computations performed by the hippocampus has been
National Brain Research Centre
limited due to paucity of knowledge on representations
from all of its input brain areas.
Two parallel processing streams, the lateral and medial
entorhinal cortex, provide non-spatial and spatial
information inputs to the hippocampus to create a
conjunctive representation of the external environment. In
turn, the lateral entorhinal cortex receives major input from
the perirhinal cortex, which is connected with unimodal
sensory areas and appears to be involved in the processing
of configurations of objects, while the medial entorhinal
cortex receives major input from the dorsal presubiculum
and retrosplenial cortex, which contain directionally
and spatially tuned neurons, and from postrhinal cortex,
which is connected with visuospatial regions of the
neocortex and has been linked to contextual processing.
Anatomically, subicular complex area has been regarded
as both an afferent and efferent area of the hippocampus.
While the subicular complex neuons receives projections
from the hippocampus; it connects to superficial layers
of the entorhinal cortex, which are the input layers to
different subfields of the hippocampus. Further, the
subicular complex region, consisting of subiculum proper,
presubiculum, postsubiculum and parasubiculum, receives
Figure2. Representative examples of firing rate maps of
sensory inputs from different cortical areas and connects to
a place X direction cell and a grid cell from the subicular
the entorhinal cortex and hippocampus, two major brain
complex area, recorded on the circular track and
areas involved in processing of spatial information. The
platform. In the colour coded rate map, red indicates
subicular complex neurons show directional and locational
>90% of the peak firing rate for that cell, blue indicates
correlates and are modulated by theta, which may act as
no firing and the intervening colours of the spectrum
internal units allowing updating of position from one
indicate successive decrements of 10% of the peak
firing rate. The subsequent columns show the firing
location to another based on the current directional
directional tuning curves and the averaged waveforms
heading. These neurons also encode head angular velocity
recorded on four channels of the tetrode.
and running speed, thus updating representation of head
direction and location. Further, anterodorsal thalamic
nuclei, containing head direction cells which encode
the current heading direction, directly connects to the
18 independently movable tetrodes to target specific
postsubiculum. Hence, the subicular complex area may
brain areas/layers, along with 2 reference electrodes
act as an interface between different brain areas involved
for neurphysiological recordings. The microdrive was
in spatial information processing in integration of spatial
stereotaxically implanted on the right hemisphere of the
and directional information. It is critical to understand the
rat's brain under surgical anesthesia, targeting subicular
network properties of subicular complex neurons, which
complex neurons. Upon postsurgical recovery, the rats
give rise to the spatial tuning and other properties of place
were subjected to behavioural training and the tetrodes
cells, to elucidate exact role of various brain regions during
lowered into the subicular complex area. Figure 1 shows
spatial memory and navigation.
the recording set-up for lowering the tetrodes while the
animal rests on the pedestal and the behavioural recording
Our laboratory uses 96-channel electrophysiology system
room with dim light, wherein the rats are trained to run
to study spatial information processing in rodent brain in
clockwise on an elevated circular track having four different
vivo, which allows recording of ongoing neural activity from
textures, placed in the centre of the room surrounded by a
large population of neurons at specific brain areas in awake
black circular curtain. Various salient distal landmarks are
freely behaving animals, through multitetrode recording
either hanged or placed on the floor at the periphery of
technique. The microdrive (multitetrode recording
the curtain. After lowering the tetrodes to the target brain
device) is custom made in the laboratory, comprising of
areas, the experimental recording sessions are carried out
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while the rat navigated clockwise on the circular track or
the grid cell shows multiple, discrete spots representing the
foraged on a circular platform. We have characterised
vertex of a triangular grid based on tessellating equilateral
various cell types within the subicular complex area and
triangles, spanning the entire environment. Currently,
their representational properties. Figure 2 shows the
the work is under progress to understand the functional
representative firing rate maps of two neurons, a place X
properties and representational dynamics amongst
direction cell and a grid cell recorded from the subicular
different subregions of the subicular complex area during
complex area. The firing directional tuning curve shows
spatial navigation.
that the place X direction cells fires at a specific location
in the environment, only when the rat approaches that
location in a particular direction, suggesting modulation
NBRC Core funds.
of spatial encoding by head directional information. While
Department of Biotechnology, Govt. of India.
National Brain Research Centre
Computational Neuroscience &
Dr. Nandini Chatterjee Singh
Prof. Prasun Kumar Roy
Dr. Pravat Kumar Mandal
Principal Investigator
Nandini Chatterjee Singh
MUSIC NETWORKS IN
Senior Research Fellow
CHILDREN WITH AUTISM
SPECTRUM DISORDER
Recent research of the typically developing brain has
Our first finding shows that in children with autism, sung
suggested that music and speech rely on distinct acoustic
words engaged a robust bilateral temporal network (Fig.
cues for processing. The speech signal has been suggested
1(a)). Interestingly, the brain networks for sung words do
to rely primarily on rapidly changing broadband sounds
not significantly differ from typically developing children
(25-30 milliseconds), whereas music patterns tend to rely
suggesting that these are robust stimuli that elicit the
on slower (200-300 milliseconds), changes in temporal
attention of children with ASD. However spoken word
information. While earlier data from our laboratory and
brain networks between ASD and TYP showed significant
others has shown speech processing deficits in children
differences (Fig. 1(b)). Spoken words elicited an atypical
with autism spectrum disorder (ASD), a large subgroup of
right frontal activation in ASD as compared to typical
individuals with ASD show exceptional musical abilities
children. Additionally we also found that the atypical
and respond to music as treatment. In particular, the
functional activation in ASD during speech perception
effects of music on social-communicative and brain
was concomitant with structural impairments in the dorsal
function are understudied. Following up on earlier work
language pathway. Given that sung stimuli are more
we are currently investigating, the processing differences
salient than spoken words and show more ‘normal' like
between speech and musical sounds in children with
patterns of activation, our results strongly advocate the
autism spectrum disorders using functional imaging and
exploration of more sung speech stimuli for entrainment
behavioural methods. The long term goals of the study
of communicative function in children with ASD especial
are to see if music entrainment alters these brain networks
those with little verbal language.
in children and if so, is it possible to use these changes to
develop specifically designed music therapy in ASD as a
Long term goals – Recent work has demonstrated the
effect of musical training on cognitive development in
recent years. Basic musical competence, acquired through
We used a sparse sampling design was developed
everyday exposure to music during development, enables
to administer spoken and sung stimuli without the
listeners to tap to musical beat, memorize, recollect and
interference of scanner noise. Speech and music networks
reproduce familiar tunes and rhythms, and experience the
in typical adults were investigated. After successfully
emotions expressed in music, regardless of formal training.
administering the paradigm to typical adults we have
Research over the past decade has highlighted that formal
extended the experiment to children with autism.
musical training also has remarkable non-musical cognitive
Sung stimuli elicit greater extent of the auditory-
benefits. Given the robust response to sung speech
communicative network than spoken words in both ASD
compared to spoken speech we propose to investigate
and typical developing children. We have collected data
whether systematic music instruction in children with
from approximately 20 children with ASD and 20 age-
autism may influence the development of communication
matched controls.
abilities in general and verbal abilities in particular.
National Brain Research Centre
Sung Words p<0.01, FDR-corrected
Spoken Words p<0.01, FDR-corrected
Largely overlapping bilateral superior and mid temporal
Right temporal activation for spoken words in ASD>TYP
activation in both ASD and TYP.
as compared to the left-lateralised activation in TYP>ASD
National Brain Research Centre
NEURAL CORRELATES
Principal Investigator
Nandini Chatterjee Singh
Junior Research Fellow
Avantika Mathur
Research Assistant
with music using North Indian classical ragas as stimuli.
Communication of emotions is crucial to social relationships
Based on Bhatkande's empirircal classification, musical
and survival (Ekman, 1992). Besides facial expression, the
stimuli comprising of instrumental renditions of Hindustani
two modalities that are often regarded as effective means
Classical Ragas were digitally recorded. Ragas were chosen
of emotional communication are vocal expression and
to induce both positive and plainitive emotional states.
music that rely on acoustic signals for their transmission
A detailed questionnaire to ascertain demographic
of messages. Neuroimaging studies in our laboratory have
information, details of music preference and training was
shown that children with autism respond more typically
administered before the survey. A website was designed to
to music as opposed to speech. Given that emotion
elicit and record participant responses on eight emotions
processing in faces and voices is impaired in children
(viz. Happy, Romantic/Tender, Devotional, Calm/soothed,
with autism our long term objective is to investigate how
Angry, Tensed/Restless, Longing/Yearning and Sad) on a
emotion contagion as applied music, is processed children
five point scale.
with autism.
Figure 2(a) shows the averaged percentage responses by
Emotional contagion is a process by which an emotion is
participants for positive (red) and plaintive (blue) ragas
induced by a piece of music because the listener perceives
played in alaap (i.e the slow non-rhythmic introductory
the emotional expression of the music and then mimics this
section of raga) while Figure 2(b) shows the effect averaged
expression internally wherein by means of either peripheral
responses for the same ragas played in gat (i.e the fast
feedback from muscles, or a more direct activation of
rhythmic composition).
relevant emotional representations in the brain, leads to an
induction of the same emotion.
The pie chart in Fig. 2(a) represents the highest rated
That Indian classical music induces different emotional
emotion for ragas played in alaap. The ragas that were rated
states is well documented and is said to evoke seven basic
‘calm/soothed (positive)' are shown by red dots and ragas
emotions: sadness, romance, peace, strength/courage,
rated ‘sad (plaintive)' are depicted by blue dots.
anger, dispassion, devotion (Bhatkande 1934). In theory,
Fig. 2(b) represents the highest rated emotion by
a raga depicting a particular emotion (bhava) could evoke
mixed and complex emotions (rasa) in a listener. While
participants for the same ragas played in gat. We see a shift
the emotional qualities of ragas have been discussed
in the rating scales. Some ragas that were rated as calm
extensively in North Indian classical music there has been
and soothing during the alaap renditions were now rated
little investigation to validate these theories.
as ‘happy' (Red dots). Similarly we see a discrimination
among different emotional states for plaintive ragas. Our
As a first approach in this area we conducted an internet
findings thereby suggest an important role for tempo in
based study to understand emotional contagion associated
emotion perception in music.
National Brain Research Centre
disorders, Front. Integr. Neurosci. 7:17. doi:10.3389/
Our preliminary findings indicate a strong correlation
between the emotions experienced by the participants and
2. Chaitra Rao, Avantika Mathur and Nandini C Singh
the intended emotion by the artist for all the ragas. Current
(2013) ‘Cost in Transliteration'–The neurocognitive he
analysis is directed at understanding the role of tempo in
Neurocognitive Processing of Romanized Writing, Brain
emotion ratings. Multiple regression analysis will be used
and Language 124, 205-212,.
to determine prominent tonic intervals and their relative
3. Arkoprovo Paul, Megha Sharda and Nandini Chatterjee
Singh (2013) Effect of Music Instruction on Cognitive
We will also use functional neuroimaging to investigate
Development: A Review. Journal of the Indian
the neural correlates underlying the perception of different
Institute of Science, 92, 441-445
emotional states.
Presentations
1. Nandini C Singh – Language and the Brain, Science
Fest, Ambedkar Centre for Biomedical Research, Delhi
University, March 2012.
2. Nandini C Singh – Speech and music in autism,
COMDEALL workshop on autism, Bangalore, May 2012.
3. Nandini C Singh – Neuro-imaging for language function
– in health and disease', Workshop on Aphasia, Indore,
August 2012.
4. Nandini C Singh - ‘Reading Assessments in a bilingual-
biscriptal setting', Maharshtra Dyslexia Association,
Mumbai, 14th February 2013.
5. Nandini C Singh – ‘Number Sense' – how cognitive
neuroscience can aid the teaching of mathematics in
schools, Cluster Inovation Centre, Delhi University, New
Delhi, 28th February 2013.
6. Nandini C Singh – ‘Singing in the Brain', Frontiers of
Speech and Music, Jadhavpur University, Kolkata, 5th
Funding
1. Research grant on ‘Development and validation of
screening tool to identify learning disability (teacher
administered screening tool', Department of Science
and Technology, 2013-14.
2. Research grant on ‘Speech and Music Processing in
Autism', from Department of Science and Technology,
3. Research grant on ‘A functional imaging study of
dyslexia in biscriptal Indian Children' from Department
of Biotechnology (2011-2014)
1. Katherine Sullivan, Megha Sharda, Jessica Greenson,
1) Dr. V. S. Mehta, Director of Neuorsciences, Paras Hospital,
Geraldine Dawson and Nandini C Singh (2013) A
Gurgaon, India.
novel method for assessing the development of speech
motor function in toddlers with autism spectrum
2) Dr. Amit Sen, Children First, New Delhi.
National Brain Research Centre
Principal Investigator
Prasun K. Roy
STOCHASTIC ACTIVATION
Research Fellow
Subhadip Paul, Rekha Varrier
AND STABILITY ANALYSIS
Project Assistant
FOR BRAIN IMAGING
Perturbation-induced activation, an emerging research field
From MRI scans [fig. 1(a)], we have developed the MRI
in computational neuroscience, offers a promising prospect
methodology for determining the texture chracteristics
to enhance the efficiency of diagnostic or therapeutic
and transport processes as tissue displacement and
applications in neuroscience. Stochastic activation, noise-
distortion, and have also estimated the temporal dynamics
aided resonance or fluctuation-induced transition, is a
of biophysical mobility parameters as conductivity and
general principle of nonlinear biological systems, and
perfusivity, as well as tensile elasticity and contextural
occurs basically due to the statistical kinetic nature of the
connectivity. We now analyse the normal brain parenchyma
components that exhibits probabilistic fluctuations of
in terms of the schema of a 2 phase media, namely
parameters. However the practical application of stochastic
intracellular and extracellular phase [fig. 1(b)]. For a porous
activation effect as a novel technique in diagnostic or
substance in a fluid (the architecture of tissue parenchyma),
therapeutic radiology has not been systematically pursued,
it is known that different transport processes----properties
and the applicability is the aim of our project.
as perfusion, conduction, permeation or deformation flow-
---are inter-related due to boundary conditions of the tissue
MRI-based Elastometric relaxation mapping of brain
geometry. We have developed a computational model of the
parenchyma with Ageing and Alzheimer's Disease:
change in elasticity and connectivity as metabolic ageing
occurs, in terms of a stochastic relaxation in fluctuation
Due to the recent looming pandemic of neurodegenerative
of the transport parameters (like diffusivity or elasticity),
diseases of ageing, one crucial y requires non-invasive
under the influence of amyloid nucleation, in terms of the
determination of the biophysical coefficients of the
latter's reaction kinetics. This amyloid formation induces
brain tissue parenchyma, such as elasticity, plasticity and
an extra inclusionary phase with stability [fig. 1(c)], and, as
topological connectivity. These indices can help develop
time elapses, our model predicts that the fluctuation of the
new mechanistic insights and offer efficient robust structural
transport parameters diminishes, while the absolute value
physics-based biomarkers. Nevertheless one may note
of the parameters approaches a fixed stationary level [fig.
that the conventional methodology of MR-based stress-
strain measurements and elastic determination of tissue parenchyma is not readily usable in the clinical domain, as
As ageing occurs, there is gradual decrease of basal
one needs to administer efficient ultrasonic deformation
energy metabolic rate, implying the transition from a non-
to the brain tissue via a piezoelectric transducer through
equilibrial state and settling towards a stationary state [fig.
the two impervious bony diploic tables of the human skull
1(d)]. The elasticity and conductivity parameters have been
(which produces irreversible signal weakening). There, one
found out using the MRI images of 48 subjects across age
also needs intricate mechanostriction-based radiofrequency
range of adulthood, 18-90 years [fig 1(e)]. The curves A
signal-acquisition and processing schemes for the scanner.
and B show the bounds of the fluctuating level of tissue
Thus an alternative MRI approach is required as a priority.
elasticity, and actually form an envelope around the mean
National Brain Research Centre
Fig. 1: (a). MRI image of brain using which the parenchymal tissue elasticity is determined from elastoporosity analysis. (b).
Normal brain tissue as hydroporous medium consisting of two phases schematically (intracellular and extracellular phases).
(c). Formation of the third phase of amyloid dystrophic neuritic domain under advanced ageing process (three temporally-
successive stages are shown vertically from top to bottom). (d). Biophysics-based theoretical model of the transition of an
elasoprous system from stationary state to high activation state (curve PQ), accompanied by increasing fluctuation in the
transport parameter (elasticity). The reverse transition, from high activation state to stationary state (curve QR), is associated
with decreasing fluctuation in elasticity. The black dots show the fluctuating descending graph at different time points. (e). The
MRI elastoporosity analysis is used to find the tissue elasticity and topographical connectivity from the scan of each individual,
the data points for 44 subjects are shown. The decreasing graph is shown in curve C, while the the evevelope curves A and B
show the bounds of the fluctuations. As ageing occurs the data points (blue squares) closely correspond to the event points
(dots) of the theoretical formulation in panel (d).
elasticity curve C, as time elapses. To paraphrase, as ageing
index , which can thus have import as a neuroimaging
process ensues, there is increasing elastoplastic relaxation,
marker. This is the first study of elastoporous ageing of brain
whereby the intracellular phase attenuates, decreasing the
parenchyma which can now be observed by ready MRI
resilence and elasticity, and the contexural connectivity
images, with incisive implications for diagnostic, screening
reduces due to the consolidation effect. As the intracellular
and monitoring utility.
space phase reduces, the phase can accommodate only
decreasing fluctuation variance that can be lodged in the
diminishing intracellular phase. The experimental data in
Enhancement of Tumour Control and Normal Tissue
fig. 1(e) can be satisfactorily accounted by our theoretical
Protection in Radiotherapy, using Neuroimaging-based
relaxation model (r = 0.88). It may be underscored that
dose perturbation protocol
we find the temporal elasticity relaxation coefficient be
The major future development of neuroimaging is
an effective rate index, the value obtained from our study
slated to be in the in the area of treatment planning and
is = 127 pascals/year. Increasing amyloid deposition, as in
optimization. Based on MRI image analysis, we have
Alzheimer's disease, would increase the elasticity relaxation
utilized the stochastic activation approach to enhance the
National Brain Research Centre
Fig. 2. (a). The 3-D surface plot of the increase of Tumour Control Probability [TCP30 (%)] as there is increase of the stochastic
fluctuation amplitude of the radiotherapy beamlet ( , in Grays per minute), the response surface also depicts the TCP
probability as there is change in the radiobiological parameter of single-strand interference by radiation ( per Gray units).
(b). Rise of of Tumour Control Probability [TCP (%)] vis-a-vis the increase of fluctuation of the radiation beamlet (f , in Rads
per minute), the third axis plots the values of the radiobiological parameter of double-strand interference by radiation ( per
Gray units). (c). Contrast enhanced T1 image of the tumour, the image is used to construct the MRI template to formulate the
radiobiological effect of stochastic radiotherapy on the neoplastic lesion. The tumour cell density is denoted by the intensity of
marker points in the third to sixth panels. The contrast MRI scan is used to segment the tumour into high active tumourogenic
zone and the necrotic central zone of very low proliferation (third panel). The successive panels show planning and modelling
contour of the tumour response after a month of stochastic fractionted radiotherapy. No marker point intensity in the last
panel, indicating satisfactory tumour containment and maximization of the Tumour Control Probability parameter.
efficiency of tumour cell elimination vis-a-vis normal tissue
the beam flux can increase the therapeutic differential of
protection under therapeutic radiology, with particular
treatment considerably, so that more malignant cells and
application to brain tumours. The major disadvantage of
less normal cells are eliminated. An important advantage
radiotherapy or chemotherapy is that the therapy agent
of this approach is that the total dose administered by the
damages both malignant tissue and normal tissue, leading
beam is not increased. In clinical settings, one selects the
to serious therapy-induced toxicity. We have investigated
most efficient radiotherapeutic schedule (out of different
the effect of radiotherapy photon on the alteration of the
types of radiotherapy protocols) by choosing one that
DNA double-strand (linear-quadratic formulation of two-
maximizes the tumour control probability formulation, yet
hit event), and the outcome of temporally perturbing
minimizing the normal cell damage.
the radiotherapy beam, done by increasing the gaussian
temporal fluctuation of the beam by means of a probabilistic
Our study shows that the increase in the level of mean-zero
function generator in the pulse circuit of the linac beam.
fluctuation of dose-rate appreciably enhances tumor control
We have shown how selecting proper perturbation
probability (TCP) in glioma, without needing dose increase
parameters (variance level and dose fraction interval) in
[fig. 2(a-b)]. The MRI image of the gadolinium contrasted
National Brain Research Centre
tumour [fig.2(c)] is used to construct therapy planning and
Science, Education & Research, Pune, April. 2012.
simulation template to formulate the radiobiological effect
3. Roy P, The Indian Brain Imaging Grid: Application to
of stochastic radiotherapy on the neoplastic lesion, the
Diagnosis & Therapy, Canada-Israel-India Trilateral
tmour is segmented into two regions: the dense shell or
Brain Roundtable and Technology Partnering Mission,
rim of actively proliferating tumour cells, which surround
Institute of Medical Research (IMRIC), Tel- Aviv, May
the central deep core with low blood supply, harbouring
the necrotic region with very less number of active tumour cells. For the radiotherapy planning and simulation, we use conformal collinear projection, so that the radiation
dose is distributed spatially or temporally across multiple
Ministry of Information Technology, Govt. of India.
pencils (6-12 in number), which converge together only
Core funds of NBRC.
on the tumour tissue, leaving the surrounding normal tissue traversed by only one pencil that which gives only
8-13% of the dose to normal tissue, effectively sparing that tissue. Our study indicates the feasibility of utilizing
I. Dr Alan Evans, Montreal Neurological Institute, McGill
Gaussian perturbation of the beam to increase tumor
control probability and normal tissue protection without
II. Dr. Manjari Tripathi & Dr P Sarat Chandra, All-India
increasing the dose administered to the patient. The
Institute of Medical Sciences, Delhi.
approach can also be applied to other antitumour modality
as radiochemotherapy, where the chemotherapeutic agent
III. Dr Ralph Martins, Edith Cowan University & CRC Mental
is activated by pulsed radiation.
Health Instt., University of Melbourne.
IV. Dr T R Seshadri, University of Delhi.
Presentation
1. Ramaswamy, R., Khanna, R., Roy, P. Effect of Ageing and
Gender on modulating the Elastic Responsivity and
I. Paul, S. Paper on "The effect of stochastic fluctuation
Topological Connectivity of the Brain, Ann. Conf. on
in radiation dose-rate on cell survival following
Magnetic Resonance Society of India, Indian Institute
fractionated radiation therapy" (Physics in Med. & Bio.,
of Technology, Bombay, Feb. 2013.
57: 1561-70, 2012) chosen as Target selection paper by
2. Varrier, R., Kondra, S., Roy, P. Developmental
Global Medical Discovery, Ottawa, Canada, for being of
Implications of Information Pathways in Brain using
importance to drug discovery process.
fMRI Perceptanalysis, Proc. International Symposium
II. Paul, S. Travelling Award for participating at Society of
on Computational Neuroscience, Indian Institute of
Neuroscience Meeting, New Orleans, 2012.
National Brain Research Centre
Principal Investigator
Prasun K. Roy
Research Fellow
Research Engineer
Comprehending how flow or transport processes occur,
neuroregenerative intervention. We develop a quantitative
whether that of energy, information, electrical current,
analysis of endogenous neurogenesis and neuronal
drugs, cells or tissue displacement, is a fundamental
migration from subventricular zone (SVZ) to the stroke
problem in basic and applied neuroscience. Conventional
penumbra zone (SPZ), and thereafter synaptogenesis and
scalar quantitative models of flow processes, have difficulty
its stabilization in target penumbra tissue, that occurs
in accounting for experimentally-observed preferential
normally to some extent in stroke patients, and this
flow in axial direction in layered tissues as brain or muscle.
restoration process can be enhanced by pharmacological
Hence, one needs a quantitative computational approach
agents. Using a preclinical rodent model for cytological or
that can clarify and predict the various transport processes
immunohistochemical studies and MRI investigations [fig.
and their modulation across the brain, vis-à-vis tissue
3(a-d)], we have developed the mathematical formulation
orientation. The recent advance of tensor neuroimaging,
of neural stem cell proliferation, neuroblast migration and
beyond simply scalar imaging, implies a broad general
its spatiotemporal mobility across brain parenchyma.
perspective towards pathophysiological processes, wherein
one can study the various transport processes or flow
parameters in the layered brain parenchyma, as chemical
Utilizing the associated NFkB pathway modulation,
diffusion, cellular permeation, electrical conduction and
we develop the cellular flow dynamics using the
information transmission. The overall objective of this
nonlinear differential equations for neural stem cell
program is to obtain basic insights and translational
formation in the SVZ. Thereafter we formulate the
implications, regarding the physiological or pathological
neuroblast migration process that is known to be
dynamics of the various transport or flow processes in the
thermodynamically coupled to the CSF flow dynamics,
brain parenchyma.
the migration occurring across the lateral ventricular wall (MRI/CSF flow imaging), and then across the orthogonal
MRI-enabled Preclinical & Clinical Approach to
fibre tracts (MRI-DTI image). We have thus elucidated an
Neuroprotective Intervention in Cerebral Stroke and
endogenous neural stem cell-based approach which deals
with cell migration using parenchymal compartment
Accounting for a tenth of worldwide mortality, stroke
analysis by incorporating (i) the principles of Michaelis-
is the leading cause of brain-related deaths, while
Menten kinetics and (ii) the chemotactic gradient-caused
the incidence of stroke's sequalae, vascular dementia,
cell mobility, so as to formulate neuroblast renewal and
is an important demographic problem in southern
its permeation. Thereafter, using allometric cytokinetic
Asia, due to increasing propensity of thromboembolic
principles, we adapted the approach to the human system,
disorders. Regarding therapy of cerebral stroke, there is
and we developed a quantitative formulation for the neural
an essential requirement of developing a quantitative
progenitor cell migration using stochastic diffusion terms
approach to optimize the performance of a translational
obtained from MRI diffusion tensor imaging [fig. 3(e)].
National Brain Research Centre
Fig. 3. (a): Development of preclinical rodent model of cerebral stroke by occluding an unilateral middle cerebral artery
under the surgical preparation. (b): Obtaining neural stem cell proliferation characteristics from subventricular zone (SVZ)
cultures. Staining of neuron on 3rd day by NeuN & GFAP. (c): Calibration scan for structural imaging of rodent stroke model.
(d): Checking unilateral arterial occlusion of rodent stroke preparation using Magnetic Resonance Angiography (MRA) by
paramagnetic Gadolinium contrast agent to delineate limitation of blood flow and constriction of a blocked arterial field
(dashed arrow) when compared with the normal arterial field of the other side (continuous arrow). (e-f): MRI diffusion imaging
to show oriented tracts (continuous arrows) that enable progenitor cell migration out from periventricular SVZ to peripheral
cortical target region in human subject (axial and coronal views), the lateral ventricles are shown by dashed arrows. (g): MRI-
based track geometry mapping, that furnishes the path length of the tracts along which the progenitor cells migrate from SVZ
to peripheral cortical region. (h): Clinical corroboration of neuro-computational model that calculates the time required for
progenitor cell migration and synaptogenesis (stroke recovery). Time duration of stroke recovery for lesion at temporoparietal
area for subject is 39 days as predicted by the mathematical model. The predicted duration is substantiated by clinical
observation of median restoration time of 5 weeks for stroke recovery of patient [arrow in panel (h), point N], the two curves
(red and blue) are respectively for sensory and motor recovery.
Thereby we have estimated (i) the migration speed of the
functionality and information transmission ensues. The
neuroblasts (ii) the path length required to be traversed by
results of the quantitative cytological and neuroimaging
the migrating neuroblasts from SVZ to SPZ, as estimated
analysis and its prediction are corroborated by data of
from MRI diffusion tensor imaging of the patient [fig.
clinical findings from neurological patient recovering
3(f-g)], (iii) the time required for the neuroblasts to move
from stroke [fig. 3(h)]. Thus we now have both animal
from SVZ to SPZ whence neurological recovery, synaptic
and human quantitative formulations of stroke recovery
National Brain Research Centre
under endogenous neurogenesis, substantiated with both
mammalian and patient findings. This model can now be
Dept. of Biotechnology, Govt. of India.
utilized to probe the enhancement of the performance of
Utrecht University Research Foundation, The Netherlands.
neurogenesis and synaptogenesis, under pharmacological
action, so as to augment the scope of regenerative therapy
in stroke and vascular dementia, utilizing the MRI-based
architecture of brain parenchyma.
I. Dr Peter Luijten, Dutch Centre for Translational
Molecular Medicine & Utrecht University.
II. Dr M V Padma & Dr T S Roy, All-India Institute of Medical
1. Kapoor S, Subramanyam V, Roy P. Optimizing
Sciences, Delhi.
performance of endogenous neural stem cell therapy
III. Dr R. K. Padhi, Indian Institute of Science, Bangalore.
for ischaemic stroke: A Neuroimaging approach to
translational medicine, International Conference on
IV. Dr Santanu Chaudhuri and Dr Raj Khanna, Indian
Neuroinformatics, Munich, Sept. 2012.
Institute of Technology – Delhi.
2. Subramanyam, VPS, Roy, P. Translational Neuroscience
V. Dr Shinjini Bhatnagar, Translational Health Science &
and imaging-guided therapy, University of Health
Technology Institute, Gurgaon.
sciences, Rohtak, April 2012.
3. Kapoor S, Subramanyam V, Roy P. Ischaemic stroke
therapy using endogenous neural stem cell strategy:
I. Kapoor, S. Travel Fellowship, Bernstein Workshop,
A validated neuroinformatics approach, NEUROCON
Technical University of Munich, Germany.
2012, Neurological Society of India, New Delhi, Dec.
II. Kapoor, S. Visiting Studentship, Utrecht University
Medical Centre, Netherlands.
4. Roy, P. Stereo Neuroimaging of Electrical Activation
Field: Source Localization using 3-D MRI Human Brain
Mapping, Indo-U.S. Workshop on Modelling Electrical
M. Tech. thesis
Activity in Physiological Systems, Indian Institute of
B. Victor, A Systems Pathway Approach to Cerebrovascular
Science Education & Research, Mohali, May 2012.
Lesions (SRM University, Chennai).
National Brain Research Centre
NON-INVASIVE MAPPING
Principal Investigator
Dr. Pravat Kumar Mandal, Ph.D
OF BRAIN OXIDATIVE
Researcher
STRESS AND pH AS
Dr. Sumiti Saharan, Ph.D
DIAGNOSTIC BIOMARKER
reduction of GSH levels in the right frontal cortex (RFC) of
Alzheimer's disease (AD) is a critical health concern,
AD female patients and in the left frontal cortex (LFC) of AD
with millions of older individuals affected worldwide.
male patients as compared to healthy young counterparts.
As such, the last decade has witnessed AD research,
focused on delineating biomolecules that reliably reflect
Recently, we also performed a comparative analysis of
AD pathology-induced alterations in the brain. Recent
GSH levels in the RFC regions of female subjects over age
research has evidenced the role of oxidative stress (OS) in
and clinical status. Our analysis demonstrated a gradual,
early AD pathogenesis, with increasing evidence that the
although non-significant, decrease of GSH levels in the
mechanisms leading to development of AD pathology, and
RFC with aging, as reflected by comparison of GSH levels
consequent neuronal death, are a result of increased OS. One
between healthy young (20-30y) and healthy old (55+y)
of the key causes for AD-pathology related increase in OS
female subjects (unpublished data, Fig. 1). The GSH levels
has been shown to be decrease in levels of the antioxidant
were found to fall noticeably in MCI patients, and were
Glutathione (GSH). GSH is a major endogenous enzyme-
further depleted in female patients with AD (Fig. 1). The
catalyzed brain antioxidant that plays a fundamental role in
GSH levels within the RFC of female AD patients were not
regulation of the intracellular oxidative state. Various in vivo
only found to be significantly lower than healthy young
transgenic animal studies as well as post-mortem analyses
female subjects, they were also significantly reduced in
of AD patient brains have reported depletion of GSH levels
comparison to healthy aged controls (unpublished data).
with progression of AD.
Our study highlights the importance of assessing in vivo GSH levels of specific brain regions such as frontal cortex,
In a pioneering study, we employed MEGA-PRESS
which are known to be susceptible to AD pathology. Early
Magnetic Resonance Spectroscopy (MRS) to assess the
detection of AD will entail identifying brain alterations due
in vivo distribution of GSH in brains in cognitively normal
to pathology at its very incipient stages. This ongoing work
human subjects as well as patients with Mild Cognitive
in our laboratory and preliminary findings suggest that
Impairement (MCI) and with AD, Using MEGA-PRESS MRS,
GSH levels in the frontal cortex may also be able to clearly
we were able to detect a clear signal of GSH in the brain. Our
distinguish MCI subjects from healthy aged subjects.
study revealed a region-specific distribution of GSH within
the brain. In addition to region-specificity, we also observed
gender dependence in GSH distribution. The mean GSH
content was found to be relatively higher in healthy
In addition to alterations in OS, our previous findings
female subjects compared to healthy male subjects, with
have shown AD-induced changes in brain pH, with the
significantly higher levels in frontal and parietal regions
left hippocampus of AD subjects showing an increase
of female subjects. Moreover, GSH levels were found to be
towards alkalinity as compared to healthy normal as well
depleted in AD in a gender-specific manner, with significant
as MCI subjects. Most brain neurochemicals, which have
National Brain Research Centre
Figure 1: In vivo detection of GSH in the brain with
MRS. Quantitative representation of alterations in GSH
concentration in the RFC of females with aging and clinical
state using MEGA-PRESS pulse sequence in 3T scanner. GSH
levels in right frontal cortex were measured for (a) healthy
26y old female; (B) healthy 56y old female; (c) 50y old MCI
female; and (d) 62y old probable AD female patient. GSH
levels were found to gradually decrease with aging. However,
Figure 2: Preliminary multi-voxel 31P MRS data showing brain
there is a further sharp decline in GSH levels associated with
pH of a healthy brain at various voxels. Data was processed
onset of MCI, and continued depletion with progression to
using in-house MATLAB programming. Color coding
AD. The GSH levels in AD patients are significantly lower from
represents pH values at different voxels as depicted in the
healthy young as well as healthy older subjects.
been reported to decrease with AD pathology, also decline
from in vivo Multi-Voxel 31P Study in Healthy Normal Young
with healthy aging. Consequently, these biomolecules may
Male/Female, Mild Cognitive Impairment, and Alzheimer's
not be reliable indicators of AD pathology onset. On the
disease. Journal of Alzheimer's disease, 31. S75-86.
other hand, brain pH has been shown to become acidic
3. Pravat K. Mandal*, Jitesh Joshi, Sumiti Saharan (2012)
with healthy aging. This inversal of pH levels, from acidic in
#. Visuospatial Perception: An Emerging Biomarker for
healthy aged individuals to alkaline in AD patients suggests
Alzheimer's Disease. Journal of Alzheimer's Disease,
that monitoring of pH levels might provide an excellent
31, S117-35.
indicator of the changing healthy aged-to-AD population.
Given the clinical significance of these findings, we have
4. Pravat K. Mandal*, Rashima Mahajan, Ivo D. Dinov
recently developed a novel methodology to map pH levels
(2012) #. Structural Brain Atlases: Design, Rationale and
in the entire brain. We have standardized the methodology
Applications in Normal and Pathological Cohorts. Journal
to measure pH in various layers of the brain using 31P MRS
of Alzheimer's Disease, 31, S169-88.
and generated a brain pH map of healthy controls (Fig. 2).
We aim to characterize the chronological changes in pH of
#These articles were IN PRESS at the time of 2011-2012 annual
different brain regions with healthy aging as well as in MCI
progress report.
Agency: Department of Biotechnology, Govt. of India
1. Pravat K. Mandal (2012) Predictive biomarkers for
Role: Principal Investigator
Alzheimer's disease using state-of-the-art brain imaging
techniques. Journal of Alzheimer's Disease, 31, S1-3.
2. Pravat K. Mandal*, H. Akolkar, and Manjari Tripathi
• Dr. Manjari Tripathi, MD, DM, Department of Neurology,
(2012)#. Mapping of Hippocampal pH and Neurochemicals
All India Institute of Medical Sciences, New Delhi.
National Brain Research Centre
INTERACTIONS OF AMYLOID
Principal Investigator
BETA PEPTIDE AND
Dr. Pravat Kumar Mandal
Researchers
ANESTHETICS: DETECTION
Bharath HNDr. Sumiti Saharan
DRUGS USING IN VIVO 19F
Magnetic Resonance Spectroscopy (MRS) has emerged
hexaflorobenzene (Fig. 3). We hope to further standardize
as an important non-invasive technique for the in vivo
and utilize this processing and quantification approach
detection of neurochemicals present in the living tissues,
for in vivo 19F quantitation from various brain regions of
including the brain. There are various molecular nuclei,
patients on fluorinated psychiatric drugs.
such as proton (1H), phosphorus (31P), carbon (13C), sodium
(23Na) and fluorine (19F), that can be detected by MRS. Due
to the near absence of any endogenous 19F signal from
brain; 19F MRS technology has found immense application
in in vivo detection and quantification of fluorinated drugs
in psychiatric disorders, such as depression. A majority
of psychiatric medications, e.g. fluoxetine, fluvoxamine,
trifluoroperazine, are fluoro-labelled. 19F MRS studies have
estimated the whole brain concentrations of fluorinated
drugs in various psychiatric patients using large single
voxel 19F MRS. Although single voxel 19F MRS enables quick
estimation of fluorine levels within the whole brain; it does
not address spatial heterogeneity in the distribution of
fluorinated drugs. The brain is not a homogenous organ and
the regional distribution of drugs within the specific brain
regions of interest (ROI) depends on several factors, such
as 1) differences in the cell type and density within the ROI,
2) differences in drug affinity to ROI, for e.g., phospholipid
Figure 3: A) Chemical structure of hexaflorobenzene,
content of tissue and the lipophilicity of the drug, and
(B) Spectroscopic imaging of the phantom containing
3) differences in vasculature and blood flow rate, etc. In
hexaflorobenzene with chloroform. (C) Shows obtained
clinical research, quantification of drug concentrations in
3×3 multi-voxel MRS signal spectra (Blue) and the fitted
different brain ROI is immensely important as it would not
spectra (Red), (D) depicts the color map of the metabolite
only enable assessment of the distribution pattern of the
concentration (in arbitrary units) for a 3×3 multi-voxel MRS.
fluorinated drugs within the brain, but also allow estimation
of drug concentration in different brain ROIs.
Financial Support
Agency: Department of Biotechnology, Govt. of India
We have addressed this issue by developing a novel Matlab-
Role: Principal Investigator
based approach for the processing and quantification of
the multi-voxel 19F signal from various ROIs at the same
time. We have successfully demonstrated the acquisition
of multi-voxel 19F MRSI signal from a phantom containing
• Dr. Rajesh Sagar, MD (Psychiatry, AIIMS)
National Brain Research Centre
Publications &
to Sonic hedgehog inhibitor SANT-1 induced apoptosis
1. Dikshit B, Irshad K, Madan E, Aggarwal N, Sarkar C,
in a Ras /NFB dependent manner. Cancer Letters.
Chandra PS, Gupta DK, Chattopadhyay P, Sinha S,
Chosdol K (2012). FAT1 acts as an upstream regulator
10. Gupta P, Ghosh S, Nagarajan A, Mehta VS, Sen E (2013).
of oncogenic and inflammatory pathways, via PDCD4,
β-defensin-3 negatively regulates TLR4-HMGB1 axis
in glioma cells. Oncogene advance online publication,
mediated HLA-G expression in IL-1β treated glioma
17 September 2012; doi: 10.1038/onc.2012.393 (joint
cells. Cellular Signaling. 7;25(3):682-689.
11. Gupta P, Dixit D and Sen E (2013).Oncrasin targets the
2. Kumar R, Andrabi R, Tiwari A, Sankaran S.P, Wig N, Dutta
JNK-NFB axis to sensitize glioma cells to TNF induced
D, Sankhyan A, Khan L, Sinha S, Luthra K (2012). A novel
apoptosis. Carcinogenesis 34(2): 388-396.
strategy for efficient production of anti-V3 human scFvs
against HIV-1 clade C, BMC Biotechnology Online
12. Ghildiyal R, Dixit D, Sen E. (2012). EGFR inhibitor BIBU
Publication, 15 November 2012; doi:10.1186/1472-
induces apoptosis and defective autophagy in glioma
6750-12-87 (joint corresponding author)
cells. Molecular Carcinogenesis. 10.1002/Inc.21938.
3. Andrabi, R, Kumar R, Bala M, Nair A, Biswas A, Wig N,
13. Tewari R, Choudhury SR, Mehta VS, Sen E. (2012) TNF
Kumar P, Pal R, Sinha S, Luthra K (2012). Production
regulates the localization of CD40 in lipid rafts of glioma
and characterization of human anti-V3 monoclonal
cells. Mol Biol Rep. 39(9):8695-9.
antibodies from the cells of HIV-1 infected Indian
14. Maharana C, Sharma KP, Sharma SK (2013) Feedback
donors. Virology Journal, 2012, 9:196
mechanism in depolarization-induced sustained
4. S. Bhutani, A. Das, M. Maheshwari, S.C. Lakhotia and
activation of extracellular signal-regulated kinase in the
N.R. Jana (2012). Dysregulation of core components
hippocampus. Sci Rep. 3:1103.
of SCF complex in polyglutamine disorders. Cell Death
15. I M Ariff, M C Thounajam, S Das, and A Basu (2013)
and Disease, 3, e428.
Japanese Encephalitis virus infection alters both
5. D. Chhangani, N.R. Jana and A. Mishra (2013).
neuronal and astrocytic differentiation of Neural Stem/
Misfolded Proteins Recognition Strategies of E3
progenitor Cells. J Neuroimmuno Pharmacology (in
Ubiquitin Ligases and Neurodegenerative Diseases.
Molecular Neurobiology, 47, 302-312.
16. V Haridas, K S Rajgokul, S Sadanandan, T Agrawal, V
6. A. Mishra, M. Maheshwari, D. Chhangani, N. Fujimori, F.
Sharvani, M V S Gopalkrishna, M B Bijesh, K L Kumawat,
Endo, A. P. Joshi, N. R. Jana and K. Yamanaka (2013).
A Basu, G R Medigeshi (2013) Bispidine-amino
E6-AP association promotes SOD1 aggresomes
acid conjugates act as a novel scaffold for the design
degradation and suppresses toxicity. Neurobiology of
of antivirals that block Japanese encephalitis virus
Aging, 4, 1310, e11-23.
replication. PLoS Neglected Tropical Diseases 7(1):
7. M. Maheshwari, A. Samanta, S. K. Godavarthi, R.
Mukherjee, and N.R. Jana (2012). Dysfunction of the
17. A Majhi, A Mahanti, K Kundu, K Dutta, A Basu, and B
Ubiquitin Ligase Ube3a May Be Associated with Synaptic
Bishayi (2013) Increased resistance of immobilized-
Pathophysiology in a Mouse Model of Huntington
stressed mice to infection: correlation with behavioral
Disease. Journal of Biological Chemistry, 287, 29949-
alterations. Brain, Behaviour, and Immunity 28:115-27.
18. Ranade Sayali, Nawaz S, Pavan Kumar R, Rose AJ,
8. J. Sharma, D. Mukherjee, S. N. Rao, S. Iyengar, S. K.
Gressens P and Mani S (2012). Early protein malnutrition
Shankar, P. Satishchandra and N. R. Jana (2013).
disrupts cerebellar development and impairs motor co-
Neuronatin mediated aberrant calcium signaling and
ordination. Br J Nutr. 107(8) :1167-75.
endoplasmic reticulum stress underlie neuropathology
in Lafora disease. Journal of Biological Chemistry,
19. Ranade Sayali, Nawaz S, Chakrabarti A, Gressens P
288, 9482-9490.
and Mani S (2013). Spatial memory deficits in maternal
iron deficiency paradigms are associated with altered
9. Dixit D, Ghildiyal R, Anto NP, Ghosh S, Sharma V and Sen
glucocorticoid levels. Hormones and behaviour.
E (2013). Guggulsterone sensitizes glioblastoma cells
National Brain Research Centre
20. Arkadeb Dutta, Niranjan Kambi, Partha Raghunathan,
Subhash Khushu, Neeraj Jain (2013). Large-scale
1. M C Thounajam, D K Kaushik, and A Basu (2013)
reorganization of the somatosensory cortex of adult
MicroRNAs in the Brain: It's regulatory role in
macaque monkeys revealed by fMRI. Brain Structure
Neuroinflammation.
Molecular
and Function. (In Press).
21. Shashank Tandon, Niranjan Kambi, Hisham Mohammed
2. D K Kaushik, and A Basu (2013) A friend in need
and Neeraj Jain (2013). Complete reorganization of the
may not be a friend indeed: role of microglia in
motor cortex of adult rats following long-term spinal
neurodegenerative diseases. CNS & Neurological
cord injuries. European Journal of Neuroscience. (In
Disorders-Drug Targets (in press)
3. N Sengupta, and A Basu (2013) Japanese Encephalitis
Virus Infection: Effect on brain development and repair.
22. Goel M, Dhingra NK (2012) Müller glia express
Current Science (in press).
rhodopsin in a mouse model of inherited retinal
4. Iyengar S (2012): Development of the Human Auditory
degeneration. Neuroscience 225: 152-61.
System. Journal of the Indian Institute of Science 92:4;
23. Katherine Sullivan, Megha Sharda, Jessica Greenson,
427-440 (Invited review), in the issue on "Development
Geraldine Dawson and Nandini C Singh (2013) A
and Disorders of the Nervous System" edited by Dr. S.
novel method for assessing the development of speech
motor function in toddlers with autism spectrum
5. Arkoprovo Paul, Megha Sharda and Nandini Chatterjee
disorders, Front. Integr. Neurosci. 7:17. doi:10.3389/
Singh (2013) Effect of Music Instruction on Cognitive
Development: A Review. Journal of the Indian
Institute of Science, 92, 441-445
24. Chaitra Rao, Avantika Mathur and Nandini C Singh
(2013) ‘Cost in Transliteration'–The neurocognitive he
BOOK CHAPTER
Neurocognitive Processing of Romanized Writing, Brain
and Language 124, 205-212,.
1. K Dutta, A. Nazmi and A Basu (2013) Japanese
encephalitis virus and human CNS infection. In
25. Pravat K. Mandal (2012.) Predictive biomarkers
Neuroviral Infections, ed S.K. Singh, D. Ruzek, CRC Pr 1
for Alzheimer's disease using state-of-the-art brain
LLc. [ISBN-10: 1439868522]
imaging techniques. Journal of Alzheimer's Disease,
26. Pravat K. Mandal*, H. Akolkar, and Manjari
Prof. Subrata Sinha
Tripathi (2012)#. Mapping of Hippocampal pH and
Use of the FAT1 gene and its products, including RNA,
Neurochemicals from in vivo Multi-Voxel 31P Study in
protein and the derivatives of the same, as suitable
Healthy Normal Young Male/Female, Mild Cognitive
molecule/s for either inflammation or cancer and the
Impairment, and Alzheimer's disease. Journal of
associated phenotype and the processes linking the same
and also as a biomarker for the above processes (PCT/
27. Pravat K. Mandal*, Jitesh Joshi, Sumiti Saharan (2012)
IB2013/050086, filed on 4 Jan 2013). (Jointly by DBT, AIIMS
#. Visuospatial Perception: An Emerging Biomarker for
Alzheimer's Disease. Journal of Alzheimer's Disease,
Dr. Ellora Sen
31, S117-35.
Granted European patent: European Pat. 2.367 784 B1–
28. Pravat K. Mandal*, Rashima Mahajan, Ivo D. Dinov
"Bicyclic triterpenoid Iripallidal as a novel anti-glioma
(2012) #. Structural Brain Atlases: Design, Rationale
and anti-neoplastic therapy in vitro". Patent granted
and Applications in Normal and Pathological Cohorts.
on 02.01.2013, International publication number (WO
Journal of Alzheimer's Disease, 31, S169-88.
National Brain Research Centre
12. Pankaj Seth: Neural Stem Cells – an in vitro model to
1. A. Das, S. Bhutani, M. Maheshwari, S. C. Lakhotia and
understand brain disorders. At Seminar Series on Stem
N. R. Jana. Dysregulation of core components of SCF
Cell Application in health care at Amity University,
complex in polyglutamine disorders. Annual Meeting
Haryana, India October, 2012.
of Society for Biological Chemists (SBCI), Kolkata, 2012.
13. Pankaj Seth: Are we doing enough to cure HIV/AIDS
in India? Seminar on HIV/AIDS and Drug Abuse, Ukrul
2. N. R. Jana. Involvement of Ube3a in cel ular protein
District, Manipur, India, November, 2012.
quality control: Implication in protein misfolding neurodegenerative disorders. NEUROCON, Kolkata, 2013.
14. Pankaj Seth, Shaily Malik and Rinki Saha: In vitro neural
stem cell system - An opportunity to "peep" inside the
3. N. R. Jana. Role of ubiquitin ligase Ube3a in the
degenerating human brain? At NeuroCon 2013 meeting
pathogenesis of Huntington's disease. Annual Meeting
at Indian Institute of Chemical Biology, Kolkatta, India,
of the Society for Neurochemistry, India (SNCI), 2013.
15. Pankaj Seth, Manju Tewari, Ankita Srivastava: Glia
4. N. R. Jana. Understanding the physiological function
Mediated Neuronal Injury in HIV-1 Neuropathogenesis:
of malin and pathogenesis of Lafora disease. Annual
"the other side of the coin" At 27th Annual Meeting of
Meeting of Society for Biological Chemists (SBCI),
Society of Neurochemistry, All India Institute of Medical
Kolkata, 2012.
Sciences, India, February, 2013.
5. D. Mukherjee, J. Sharma, S.N Rao, S. K. Shankar, P.
16. Shaily Malik, Rinki Saha and Pankaj Seth. "Modulation
Satishchandra and N. R. Jana. Neuronatin mediated
of human neural precursor cell proliferation and
altered calcium signalling and ER stress cause
differentiation by HIV-1 transactivating protein, Tat and
neuropathology in Lafora disease. Annual Meeting of
drugs of abuse". 18th Annual Scientific Conference of
Society for Biological Chemists (SBCI), Kolkata, 2012.
Society on Neuroimmune Pharmacology, Hawaii, USA.
6. N. R. Jana, J. Sharma, D. Mukherjee, S. N. Rao, S. K.
Shankar and P. Satishchandra. Neuronatin mediated
17. Manju Tewari. Role of Glial cells in HIV-1
aberrant calcium signaling underlie neuropathology
neuropathogenesis. At NeuroCon 2013 meeting at
in Lafora disease. Annual meeting of the Society for
Indian Institute of Chemical Biology, Kolkatta, India,
Neuroscience (SFN), New Orleans, 2012.
January 2013.
7. Pankaj Seth: Neural Stem Cells - a Tool for Basic Research.
18. Ellora Sen. Inflammation mediated oxidative stress in
At Amity University, Haryana, India, April, 2012.
cancer. 4th International Congress on Cell Membrane
8. Pankaj Seth, Pretty Garg and Manju Pant Tewari. Role
and Oxidative Stress, Suleyman Demirel University,
of Neuron Glia Crosstalk in HIV-1 Neuropathogenesis.
Isparta, Turkey. June 2012. Invited lecture and Session
11th International Symposium on Neurovirology and
2012 Conference on HIV in the Nervous System. New
19. Ellora Sen. HLA gene regulation in glioma: Role of
York, USA, May, 2012.
Inflammation. Indian Association of Cancer Research,
9. Pankaj Seth in Calendar of Events of National Institutes
New Delhi, February, 2013.
of Health (NIH)): Neuron - Glia interactions during HIV
20. Deobrat Dixit. Guggulsterone sensitizes glioblastoma
Neuropathogenesis. National Institutes of Health (NIH),
cells to Sonic hedgehog inhibitor SANT-1 induced
Bethesda, USA, May, 2012.
apoptosis.Emerging Trends and Challenges in Basic and
10. Pankaj Seth: Neural Stem Cells - a window into
Translational Research in Biochemistry, Department of
neurodegenerative diseases. At Rajiv Gandhi Institute
Zoology, Banaras Hindu University, Varanasi, Feruary
of Technology, Amethi, During National Seminar on
"Stem Cell an emerging Healthcare Frontier" during
21. Ellora Sen. TNF regulates resistance to apoptosis
in glioblastomas. 3rd International Cancer Research
11. Pankaj Seth : HIV-1 Induced Neuronal damage: Who is to
Symposium, Kolkata, December 2012.
be blamed? At XXX Annual meeting of Indian academy
22. Ellora Sen. Inflammation and resistance to apoptosis in
of neurosciences, Guru Nanak Dev University, Amritsar,
gliomas: The rehabilitation of thoughts. Carcinogenesis,
India, Oct, 2012.
New Delhi, November 2012.
National Brain Research Centre
23. Deobrat Dixit. Inhibition of G9a in glioma cells inhibits
35. A Basu (2013) Neuronal Innate Immune Response in
hypoxia signalling and induces cell death through
Japanese Encephalitis Virus infection. 3rd Molecular
apoptosis and autophagy. Carcinogenesis, New Delhi,
Virology Forum meeting, National Institute of Virology,
November 2012.
Pune, 10-11th January 2013. (Invited speaker)
24. Fahim Ahmad. Identification of signalling circuitries
36. A Basu (2012) Krüppel Like Factor 4 in neuro-
regulating telomerase activity in glioma. Carcinogenesis,
inflammation: a new therapeutic target? BioWorld 2012,
New Delhi, November 2012.
Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, 10th-12th December,
25. Piyushi Gupta. β-defensin-3 negatively regulates TLR4-
2012. (Invited speaker)
HMGB1 axis mediated HLA-G expression in IL-1 treated
glioma cells. Carcinogenesis, New Delhi, November
32. D K Kaushik, M C Thounajam, and A Basu (2012) Kruppel
Like Factor 4 regulates microglial activation in response to Interleukin-1. XXX Annual Meeting of Indian
26. Sadashib Ghosh and Ellora Sen. TNF induced HIF-
Academy of Neurosciences, 27th-30th October, 2012,
1- catenin axis regulates MHC class I gene activation.
Carcinogenesis, New Delhi, November 2012.
33. A Nazmi, I A Mohammed, K Dutta, K Kundu, and A Basu:
27. Ghildiyal R. Inhibition of EGF Receptor by BIBU induces
Neural Stem/Progenitor Cells induces conversion of
apoptosis and defective autophagy in glioma cells.
encephalitogenic T-cells into CD4+-CD25+- FOXP3+
Carcinogenesis, New Delhi, November 2012.
Regulatory T-cells. XXX Annual Meeting of Indian
28. Deobrat Dixit. Inhibition of Ras /NFB axis sensitizes
Academy of Neurosciences, 27th-30th October, 2012,
glioblastoma cells to Shh inhibitor induced apoptosis.
Indian Academy of Neuroscience, Amristsar, October
34. A Nazmi, K Dutta, K Kundu, and A Basu : TLR7 regulates
expression of suppressor of cytokine signaling (SOCS)
29. Ellora Sen. Hypoxia-Inflammation nexus: A potential
in CNS post Japanese Encephalitis Virus infection. XXX
anti-glioma target? Indian Society of Neuro-Oncology
Annual Meeting of Indian Academy of Neurosciences,
(ISNOCON), NIMHANS, Bangalore, April, 2012.
27th-30th October, 2012, Amritsar
35. A Basu :Basic and Translational Studies at the Host-
30. S.K. Sharma and C. Maharana. Mechanisms of pattern-
Pathogen Interface. UGC refresher courses for
dependent activation of extracellular signal-regulated
college and university faculty members, Center for
kinase in the hippocampus. Society for Neuroscience
Biotechnology, JNU, 20th July, 2012
meeting, Oct. 13-17, 2012, New Orleans, USA.
36. A Basu: Therapeutic targeting of Krüppel like factor 4
31. Kiran Pandey and Shiv K. Sharma. HDAC inhibition
abrogates inflammation and oxidative stress in brain.
facilitates surface recruitment of AMPA receptors in the
4th International Congress on Cell Membrane and
hippocampus. XXX Annual Meeting of Indian Academy
Oxidative stress. 26th-29th June.
of Neurosciences, 27-30 October, 2012, Guru Nanak Dev University, Amritsar.
Suleyman Demirel University, Isparta, Turkey. (Invited speaker)
32. A Basu (2013) The transcriptional regulation of
37. A Basu: Antiviral and Neuroprotective Role of
microglial function: the tightrope walk of CNS
Octaguanidinium Dendrimer-Conjugated Morpholino
innate immune response. Society for Neurochemistry
Oligomers in Japanese Encephalitis. 9th International
Meeting 2013, AIIMS, New Delhi, 21-23rd February.
Symposium on Polymer Therapeutics: From Laboratory
(Invited speaker)
to clinical practice 28th -30th May, 2012, Valencia, Spain.
33. A Basu (2013) Host pathogen interaction in Japanese
(Invited speaker)
Encephalitis Virus infection: from bench to bedside.
38. Ranjit K. Giri. Utilization of Neurosphere Culture in the
South Asian University, New Delhi, 8th February, 2013.
Development of a Novel in vitro model of Alzheimer's
(Invited speaker)
Disease, McLaughlin Research Institute, Great Falls,
34. A Basu (2013) An introduction to Psychoneu-
Montana, USA, 2012.
roimmunology Preconference workshop (Neurocon
39. Sourav Banerjee: Tune it up: Modulation of neuronal
2013), IPGMER, Kolkata, 17th January, 2013. (Invited
circuitry and synaptic mechanisms of plasticity. IISER
Pune. August 2012.
National Brain Research Centre
40. Soumya Iyengar: Organization of the Vertebrate Nervous
51. Nandini C Singh - ‘Reading Assessments in a bilingual-
System. Fourth DST-SERB school in Chronobiology,
biscriptal setting', Maharshtra Dyslexia Association,
North-Eastern Hill University (NEHU), Shillong, June 20,
Mumbai, 14th February 2013.
52. Nandini C Singh – ‘Number Sense' – how cognitive
41. Soumya Iyengar: Comparative Aspects of Brain
neuroscience can aid the teaching of mathematics in
Evolution - Mammals versus Birds. Fourth DST-SERB
schools, Cluster Inovation Centre, Delhi University, New
school in Chronobiology, North-Eastern Hill University
Delhi, 28th February 2013.
(NEHU), Shillong, June 21, 2012.
53. Nandini C Singh – ‘Singing in the Brain', Frontiers of
42. Soumya Iyengar: Auditory System – I. Sixth DST-SERB
Speech and Music, Jadhavpur University, Kolkata, 5th
School in Neuroscience, National Institute of Science
Education and Research (NISER), Bhubaneswar, Orissa, December 18, 2012.
54. Ramaswamy, R., Khanna, R., Roy, P. Effect of Ageing and
Gender on modulating the Elastic Responsivity and
43. Soumya Iyengar: Auditory System – II. Sixth DST-SERB
Topological Connectivity of the Brain, Ann. Conf. on
School in Neuroscience, National Institute of Science
Magnetic Resonance Society of India, Indian Institute
Education and Research (NISER), Bhubaneswar, Orissa,
of Technology, Bombay, Feb. 2013.
December 18, 2012.
55. Varrier, R., Kondra, S., Roy, P. Developmental
44. Soumya Iyengar, Arvind Singh Pundir, Bishan
Implications of Information Pathways in Brain
Radotra, Praveen Kumar, PC Dikshit, SK Shankar, Anita
using fMRI Perceptanalysis, Proc. International
Mahadevan. Development of excitatory neural circuits
in the human auditory cortex. Poster presented at The
Indian Institute of Science, Education & Research, Pune,
8th FENS Forum of Neuroscience, Barcelona, Spain, 14 -
18 July, 2012.
56. Roy P, The Indian Brain Imaging Grid: Application to
45. S Dagar, NK Dhingra. Loss of photoreceptors in rd1
Diagnosis & Therapy, Canada-Israel-India Trilateral
mouse leads to selective upregulation of amacrine cell-
Brain Roundtable and Technology Partnering Mission,
specific synaptic protein mRNAs. Annual Conference of
Institute of Medical Research (IMRIC), Tel- Aviv, May
the Indian Academy of Neurosciences (Amritsar, India;
October, 2012).
57. Kapoor S, Subramanyam V, Roy P. Optimizing
46. V Jain, E Ravindran, R Guruswamy, NK Dhingra. Expression
performance of endogenous neural stem cell therapy
of Melanopsin and its co-expression with Brn3b
for ischaemic stroke: A Neuroimaging approach to
alters in Mouse model of Retinal Degeneration FASEB
translational medicine, International Conference on
summer research conference on Retinal Neurobiology
Neuroinformatics, Munich, Sept. 2012.
and Visual Processing (Steamboat Springs, CO, USA; Jul-Aug, 2012).
58. Subramanyam, VPS, Roy, P. Translational Neuroscience
and imaging-guided therapy, University of Health
47. NK Dhingra, A Ghosh. Loss of Photoreceptors in rd1
sciences, Rohtak, April 2012.
Mouse is Associated with Upregulation of GABAC Receptors in Inner Retina. ARVO meeting (Fort
59. Kapoor S, Subramanyam V, Roy P. Ischaemic stroke
Lauderdale, USA; May, 2012).
therapy using endogenous neural stem cell strategy: A validated neuroinformatics approach, NEUROCON
48. Nandini C Singh – Language and the Brain, Science
2012, Neurological Society of India, New Delhi, Dec.
Fest, Ambedkar Centre for Biomedical Research, Delhi
University, March 2012.
60. Roy, P. Stereo Neuroimaging of Electrical Activation
49. Nandini C Singh – Speech and music in autism,
Field: Source Localization using 3-D MRI Human
COMDEALL workshop on autism, Bangalore, May 2012.
Brain Mapping, Indo-U.S. Workshop on Modelling
50. Nandini C Singh – Neuro-imaging for language function
– in health and disease', Workshop on Aphasia, Indore,
Indian Institute of Science Education & Research,
August 2012.
Mohali, May 2012.
National Brain Research Centre
Distinctions, Honours
and Awards
DISTINCTIONS, HONOURS AND AWARDS
Details of Ph.D. students who have obtained Degree along with Title of Thesis
Name of candidate
Date of Award Enrolment
Title of the thesis
of Degree
Dr. Chinmoyee Maharana
Activity-Dependent Posttranslational Modifications of Proteins:
Implications for Synaptic Plasticity and Memory
Dr. Parthiv Haldipur (2005)
The role of Sonic hedgehog signaling in the proliferation and
differentiation of cerebellar granule cell progenitors
Dr. Jai Prakash Sharma (2005)
Identification and characterization of substrates of malin, an E3
ligase mutated in Lafora progressive myoclonus epilepsy
Dr. Sudheendra Rao N R
Protein aggregation, sequestration and ubiquitin proteasome
system dysfunction in the pathogenesis of Lafora disease
Dr. D. Lalitha (2005)
Redox signaling mechanisms and altered gene expression
mediated by dopaminergic neurotoxin, MPTP : Implications
in Parkinson's disease
5. Ms. Suhela Kapoor, Integrated Ph.D. 2007 student
1. Dr. Anirban Basu: F1000 Faculty Member of the Year
Visiting Studentship, Utrecht University Medical Centre,
Award' for the Faculty of Neurological Disorders-2012*
*The awards recognize Faculty Members who have made
6. Ms. Megha Sharda, Integrated Ph.D. 2007 student was
the most significant contribution to the F1000 service over
awarded for attending the Society for Neuroscience
the past year, as judged by their editorial team.
2012 at New Orleans, U.S.A. from 13th October, 2012 to
2. Dr. El ora Sen: Shakuntala Amir Chand Award, 2009, Indian
17th October, 2012.
Council of Medical Research (ICMR), awarded 2013
7. Mr. Subhadip Paul, Ph.D. 2005 student Paper on "The
3. Dr. Ellora Sen: Elected member of Guha Research
effect of stochastic fluctuation in radiation dose-rate on
Conference (GRC), 2012
cell survival following fractionated radiation therapy" (Physics in Med & Bio, 57: 1561-70, 2012) chosen as
Target selection paper by Global Medical Discovery, Ottawa, Canada, for being of importance to drug
1. Ms. Megha Sharda, Integrated Ph.D. 2007 student was
discovery process.
awarded for attending International Meeting for Autism
Research (IMFAR 2012), Sheraton Centre at Toronto,
8. Mr. Subhadip Paul, Ph.D. 2005 student was awarded
Canada from 17th May, 2012 to 19th May, 2012.
for attending the Society for Neuroscience 2012 at New Orleans, U.S.A. from 13th October, 2012 to 17th
2. Ms. Shaily Malik, Integrated Ph.D. 2007 student was
awarded for attending the 18th Annual Scientific
October, 2012.
Conference at Honolulu, HI from 24th April, 2012 to
9. Ms. Megha Maheshwari, Integrated Ph.D. 2007 student
28th April, 2012.
was awarded for attending the Society for Neuroscience
3. Mr. Apoorv Sharma, Ph.D. 2008 student was awarded
2012 at New Orleans, U.S.A. from 13th October, 2012 to
for Conference in Technische University, Miinchen,
17th October, 2012.
Arisstrape 21, 80333 Miinchen, Germany from 07th
10. Dr. Gouri Shanker Patil, Post Doctoral Fellow received
September, 2012 to 08th September, 2012.
the MUKTESH AWARD for Best Paper in Speech for the
4. Ms. Suhela Kapoor, Integrated Ph.D. 2007 student was
scientific paper titled "The lexical iconicity in Indian Sign
awarded for attending the Neuroinformatics 2012
Language" at the 45th National Conference of Indian
Congress, Germany from 06th September, 2012 to 15th
Speech and Hearing Association held at Chennai from
September, 2012.
01st to 03rd February, 2013.
National Brain Research Centre
COURSE-WORK
Ms. Utkarsha A Singh: Integrated Ph.D. student, has been
Mr. Kautuk Kamboj: Ph.D. student, has been awarded first
awarded first rank upon completion of course work during
rank upon completion of course work during the year 2012
the year 2012 and a certificate was given to her on the 9th
and a certificate was given to him on the 9th Foundation
Foundation Day, the 16th December 2012.
Day, the 16th December 2012.
Ms. Pooja Parishar: Integrated Ph.D. student, has been
Mr. John Thomas: Ph.D. student, has been awarded second
awarded second rank upon completion of course work
rank upon completion of course work during the year 2012
during the year 2012 and a certificate was given to her on
and a certificate was given to him on the 9th Foundation
the 9th Foundation Day, the 16th December 2012.
Day, the 16th December 2012.
She has also been awarded for the Comprehensive Viva of
Course-Work during the same year.
National Brain Research Centre
Externally Funded
EXTRAMURAL FUNDING DURING 01-04- 2012 - 31.03.2013
Name of Project
Principal
Sanctioning
Sanctioned
Project No.
Sanction
Dementia Programme
Role of CNS Opportunistic infections
$104,706.00 PKS/NIHRO-
in subsequent Development of HIV
Delcon (E- Library Consortium) Project
Understanding Signaling Circuitries
involved in glioma
Study the neuroprotective role of
ubiquitin ligase, E6-AP in the transgenic
mice model of Huntington's disease
Opioid modulation of motivated
behaviours in male zebra finches
Study the defect in neurogenesis and
initial synapse formation in mouse
model of angelmen mental retardation
To elucidate the role of inflammasomes
and other molecular events leading to
Hypoxia induced Neuroinflammation
Two Photon microsope facility for
advance research in basic neuroscience
and unraveling the mechanism of brain
Understanding the physiological
function of malin, a ubiquitin ligase
mutated in Lafora's progressive
myoclonus epilepsy
A Functional imaging study of dyslexia in NANDINI C. SINGH
biscriptal Indian children
C.S.I.R. -II Study the role of Natural
immune response in JEV infection
Natural Network Mechanism in subicular YOGANARASIMHA
complex neurons during spatial,
navigation and learning in awake
behaving rats.
Centre for Epilepsy Project (M.E.G.)
Brain Mechanism of Tactile Perception
Perception Engineering Programme
National Brain Research Centre
Role of human umbilical cord blood
stem and neural stem cells in neuronal
regeneration and functional restoration:
A comparative study in male adults rats
with acute spinal cord injuries
India Intergration with Global Imaging
System via MCGill Linkage (NKN)
Neurobiology and understanding
circadian system linkage of cognitive
performance in an avian model system
Host Directed Drug Targeting Implication ANIRBAN BASU
of suppressors of cytokine signaling
Collaboration for translation & Clinical
Research Between Translational Helth
science and technology institue (glue
ICMR HIV Associated neurocognitive
PRAVAT K. MANDAL BITS PILANI 14.12.2011
Investigation of the relationship between CHAITRA RAO
literacy instruction and metalinguistic
awareness in adults
Identification of associations between
genetic variants in the neural migration
pathway and behavioral correlates of
dyslexia linking genes and behaviour
using familial and sproadic cases.
Speech and music processing in
Autism Spectrum Disorder A functional
neuroimaging study
Understanding Neuron -Glia Crosstalk in PANKAJ SETH
HIV Research in Health and Disease
National Initiative on glial cell research in SHIV KUMAR
health and disease
Pulse Seqence (invivo) and processsing
PRAVAT K. MANDAL D.B.T.
scheme development for Anethetics and
amyloid beta petide interactions using
Connectivity and role of inhibitory
Well Come 30.03.2012
neurons in auditory perception DBT/
BANDHYOPADHYAY Trust
Welcome Trust Alliance
Using Stereo X-Ray image to develop a
ready automated method for screening
of Alzheimer type mild cognitive
impairment from normal ageing in
resource constrained setting
Ramalingaswamy fellowship 2011-12
National Brain Research Centre
Neuroscience education research
fellowships in clinical neuroscience
and Neuro-informatics & Computatinal
DST INSPIRE Fellow
Development and validation of screening NANDINI C. SINGH
tool to Identify learning disability
Using Peptidomimetics to design
small molecules from a novel P1
Neuroplasticity and Language
Anatomical Correlates of Vedic Recitation
National Brain Research Centre
DISTRIBUTED INFORMATION CENTRE (DIC)
detection system, gateway level antivirus, VPN facility,
The Distributed Information Centre (DIC) manages the
managing IT policy and detailed auditing and logging.
complete Information & communication Technology
The VPN facility provides NBRC users facility to access
(ICT) requirements of the Institute. It manages the core
internal resources of the institute from remote locations
computing and networking infrastructure of the institute
in a secure manner.
thus aiding the academic and research activities at NBRC.
The DIC staff actively provides technical and scientific
DATACENTER AND SERVER FACILITY
support to researchers in their computational requirements.
• The institute has a modest datacenter facility for
It also undertakes development of software applications
housing the core network and server infrastructure
for scientific as well as administrative departments thus
having precision climate control, redundant power
facilitating e-Governance in the organization. We are
and UPS supply, clean agent based fire detection and
also planning to develop an in-house program for Online
suppressant system.
Tracking System that would automate monitoring the
• The institute manages an in-house hosting of all core
movement and processing of all files in near future.
servers for DNS services, Web servers, Email servers etc.
The IT infrastructure is constantly upgraded as per
for the official domains of the institute (i.e. www.nbrc.
the growing needs of the Institute and technological
ac.in and www.nbrc.res.in ). In addition it also provides
advancement in the field. Some of the critical IT
hosting services for Indian Academy of Neurosciences
infrastructure of the Institute is listed as under:
(www.neuroscienceacademy.org.in) and Society of
Neuro Chemistry, India (www.snci.nbrc.ac.in) as a
service to neuroscience community of the country. All
NETWORK INFRASTRUCTURE
the public servers have nearly cent percent uptime and
are efficiently maintained with detailed logging and
• The core network of the institute is running on managed
switching infrastructure with a fiber optic backbone
of 10Gbps with redundant paths. The network is
• The DIC also manages a pool of application servers
segmented into multiple virtual LAN's to segregate
running on Windows and Linux platforms for providing
unrelated traffic and ensure security. The core network
application services to students and researchers
is further integrated with campus wide wireless
apart from dedicated application servers of different
network providing secure and authenticated access to
authorized users. The uptime of the entire core wired
and wireless network is monitored round the clock.
UPCOMING AND ONGOING ACTIVITIES
• The institute is part of National Knowledge Network
• The DIC has recently expanded the core network to the
(NKN) of Government of India and is connected with NIC-
new Institutional Building (IB-1) apart from upgrading
Delhi over a high speed gigabit fiber optic connectivity,
the wireless network.
certain research projects utilizing the NKN are already
• DIC is also planning to implement unified
operational and some other are being implemented
communication services thereby integrating data and
thus directly aiding in the research activity of NBRC. The
voice networks with the planned implementation of IP-
institute also has a redundant radio link for maintaining
PBX facility to fulfill Government of India regulations.
essential network services.
• The upgradation of ageing core servers to blade servers
• The institute has secure firewall and unified threat
and implementation of cross-site DR site for essential
management appliances for network safety, intrusion
service and data is being planned.
National Brain Research Centre
ANIMAL FACILITY
transgenic, knock out and mutant mice are housed under
NBRC, an autonomous institute of the Department of
germ-free conditions in filter top cages and individually
Biotechnology, has the mandate of carrying out frontline
ventilated cages (IVC). Such animals are handled in laminar
research to understand neurobiology of brain disorders.
hoods, and the moved to fresh cages in cage-changing
In order to help fulfilling this mandate, NBRC maintains a
station under hepa-filtered air.
state of the art animal facility to meet the requirements
The animals are maintained under controlled environmental
of the scientists for advanced neuroscience research. The
conditions as specified in CPCSEA guidelines, with
Institute recognizes that the use of laboratory animals in
temperature maintained between 22
research is an important privilege accompanied with a
2C, relative
humidity between 45-55%, 12:12 hr light-dark cycle, and
great ethical responsibility to ensure humane care and
12-15 air changes per hour. The air-handling system uses
use of these valuable subjects. To ensure appropriate
100% fresh air for each change. Qualified and trained
care and use detailed programs of the best veterinary
veterinarians oversee all the animal health concerns, and
and husbandry care, and programs for the peer-reviewed
provide all necessary veterinary care to ensure that healthy
evaluation of all activities prior to the use of any animal in
animals are available for research.
research are in place. NBRC is committed to the highest
standards of research and recognizes that laboratory
All animals are procured as per CPCSEA guidelines. A health
animals must receive the best possible care, not only to
surveillance program for screening incoming animals is
obtain valid research data, but also to ensure the health
carried out to assess animal quality. Animals procured
and safety of animals, researchers and animal caretakers.
from other places are kept in quarantine for appropriate
The Animal Facility is registered with the Committee for
length of time. An effective quarantine minimizes risk for
the Purpose of Control and Supervision of Experiments on
introduction of infection in established colony.
Animals (CPCSEA), Ministry of Environment and Forests,
Government of India, New Delhi (Registration number:
The animal facility has a state-of-art surgical suite equipped
464/a/CPCSEA, dated 24/08/2001). All activities of the
with intensity controlled surgical lights, advanced surgical
animal facility are carried out as per standard operating
microscopes, gas anesthesia machines, equipment
procedures (SOPs). The Animal Facility maintains records
for monitoring the physiological state of the animals,
of day-to-day activities as well as breeding, maintenance
including heart rate monitor, pulse oximeter and rectal
and experimentation on the animals as per statutory
thermometer. For cleaning and sterilization of the surgical
requirements of CPCSEA.
instruments there is an ultrasonic instrument cleaner,
glass bead sterilizer and ethylene oxide gas sterilizer. The
The main responsibility of the Animal Facility is to procure
animal facility has a necropsy room, perfusion room with
and breed laboratory animals as required, and supply
a perfusion hood, deep freezer for carcass storage, and
quality animals to in-house researchers, which are used
incinerator for disposal of the animal carcass.
as animal models for understanding the human brain in health and disease. Staff of the animal facility ensures
Animal facility has been equipped with a card reader
humane and appropriate animal care. A high degree of
security system. The access is restricted to the animal
hygienic conditions are maintained in the animal house
house staff, maintenance staff and the investigators who
by regular cleaning and sterilization of the cages, water
are listed in the IAEC approved protocols. All the personnel
bottles, bedding and feed. The animal rooms are also
who handle animals are required to have a current tetanus
regularly disinfected. Heavy-duty steam autoclaves have
vaccination, and those who handle non-human primates
been installed for these purposes. The staff is required to
(NHP) are screened for tuberculosis. Everyone handling
take shower and change to work-overalls before entering
NHP's is trained in the procedures for the first-aid in case of
the animal rooms, and again in the evening after finishing
an injury from an animal bite or scratch.
the work. All users wear facemasks and gloves before handling animals.
Close circuit monitoring cameras have been installed
at various locations in the facility to help in effective
All animals are housed in species appropriate cages,
monitoring of the animal facility.
which are designed as per the CPCSEA guidelines. The
outdoor play area for non-human primates has six large
The Veterinary staff of animal facility conducts a training
interconnected enclosures that provide a flexible layout
program for Integrated-Ph.D. and Ph.D. students & the
for optimising enrichment and social interactions. The
Project Assistants in laboratory animal science covering
National Brain Research Centre
ethical guidelines that regulate scientific experiments on
Knock Out Mice
animals, general biology and reproduction of the laboratory
• UBE3A null mice (Angelman syndrome model)
animals, animal identification techniques, approved
methods of blood collection, injections, anesthesia and
Mutant Mice
monitoring, handling and restraint, husbandry, care, sex
• CBA/J mice (Retinal degeneration model)
differentiation, humane euthanasia etc. Special emphasis
is on health management, identification and management
of pain in the animals.
• Long Evans• Sprague Dawley
The animal facility is currently maintaining the following
species and strains of the laboratory animals.
Rabbits
• New Zealand white
Mice Strains
• Rhesus Monkeys (Macaca mulatta)
• Bonnet Monkeys (Macaca radiata)
• C57BL/6J• CD1
Transgenic Mice
• Zebra finches (Taeniopygia guttata)• House crows (Corvus splendens)
• B6C3-Tg (APP695)85DboTg(PSEN1)85Dbo (Alzheimer
• Jungle crows (Corvus levaillantii)
• UBC-GFP (Green fluorescent protein)
All the mice strains are maintained by inbreeding and
• B6CBA-Tg (Hdexon1) 62Gpb/3J (Huntington disease
the rat strains by out-breeding. Zebra finch colonies are
maintained by out-breeding. The transgenic and knockout
mice are maintained under a specialized breeding program
• B6.Cg – Mapttm1 (EGFP) KltTg (MAPT) 8cPdav/ J
after the investigators provide the molecular genotyping
(Alzheimer disease model)
of these strains based on presence or absence of the gene
• B6.129P2-Gsk3btm1 Dgen/J (Alzheimer disease model)
of interest.
National Brain Research Centre
The NBRC Library plays a vital role in the collection,
A total of 115 registered users including scientists,
development and dissemination of scientific and technical
researchers, students and other staff used the NBRC library
information to meet the present and future needs of the
facilities in the past year. The NBRC Library also provides
centre and also provides facilities and support to the
"Inter Library Loan" Services to NBRC's 48 networked
scientists, researchers, students, staff and NBRC's networked
centres all over India. Researchers at different centres send
their requirement for research material or journal articles
through email to NBRC Library which are then downloaded
The NBRC library has a large collection of Journals, books
and sent to them free of cost. The library entertains an
and other relevant research materials on Neuroscience,
average of approximately 448 requests for articles and this
Biochemistry, Genetics, Molecular Biology, Immunology &
number is increasing every year.
Microbiology, Pharmacology and Toxicology, Psychology,
Physics, Mathematics, Computer Science and General
The NBRC Library regularly evaluates its information
Subjects. The NBRC Library currently subscribes to 16
services to ensure that the Institution's requirements
journals, and also subscribes to 963 online journals through
are met. It promotes resource sharing and cooperation
the DBT e-Library Consortium (DeLCON). It also maintains
activities among libraries by providing an efficient and
digital archives and news clips about the centre and
reliable means of resource sharing, that is, the inter library
subscribes to Newspapers and News Letters. The collection
loan for the maximum use of resources, by providing
of the NBRC Library is growing day-by-day along with new
copies of documents which are not available to researchers
developments in research and knowledge in the field of
at centres outside the institute.
Neuroscience and related areas.
MAIN ACTIVITIES OF NBRC LIBRARY
1. Book Acquisition
To provide optimum service to all users, the NBRC library is
2. Periodicals Acquisition
currently digitizing its list of collections using the LSEASE
3. Selective Dissemination Information (SDI),
software, to which all users will have full access. A barcode
technology has also been installed for accurate and speedy
4. Current Awareness Services (CAS)
circulation and the management of all library documents.
5. Inter Library Loan
The new software will also help in efficient library operations
6. Resource Sharing
viz. administration, acquisition, circulation, serial control,
7. Circulation services
cataloguing and information retrieval.
8. Reference Services, Bibliographic services
The Library has set up 22 IBM PC-Pentium-IV Computers
9. Indexing and Special Services
with ISDN Internet facility to provide services for use of
10. Collects maintains, store and retrieves information
researchers and students in the NBRC Common room and
and data keeping in the view of evolving needs of its
has been providing electronic access to the subscribed
journals within the campus portal.
11. Help to Network Centres.
National Brain Research Centre
DBT's Electronic Library
8. Rajiv Gandhi Centre for Biotechnology (RGCB) –
A National-level Multi-institutional Initiative for
Information Resources in the Life Sciences
9. International Centre for Genetics and Engineering
Biotechnology (ICGEB), New Delhi
The ‘DBT's Electronic Library Consortium (DeLCON)' is a
significant initiative of the Department of Biotechnology
10. National Agri-Food Biotechnology Institute, Mohali,
(DBT), Govt. of India, to enhance informational resources
in its research Institutions. It was launched in January, 2009
11. National Institute of Biomedical Genomics, Kalyani,
with the ten DBT member-institutions with a large number
of prominent journals. It is a topical endeavour for providing
access to scholarly electronic resources including full-text
12. Regional Centre for Biotechnology, Gurgaon
and bibliographic databases in all the life science subject
13. Transnational Health Science & Technology, Institute,
disciplines to the DBT institutional community across the
country. It facilitates access to high quality e-resources to
14. Department of Biotechnology (DBT) Head Quarters,
the research institutions to enhance research, teaching and
15. National Institute of Animal Biotechnology, Hyderbad
The access to all major e-resources was enabled in the
beginning of 2009. It has now been extended to new 17
more institutions in 2nd phase of extension in 2010 and
Institutions from North Eastern region
further 7 members have been added in the 3rd phase of
16. Indian Institute of Technology, Guwahati, Assam
extension in 2011. Last year, there emerged the enlarged
17. North Eastern Regional Institute of Science &
DeLCON Consortium with 33 members. Besides the DBT
Technology, Arunachal Pradesh
institutions, an emphasis has been given to incorporate
institutions and universities (both in the state and central
18. Dibrugarh University, Assam
govt. sectors) across the states in North Eastern India.
19. Assam University, Silchar
DeLCON provides current as well as archival access to more
20. North East Institute of Science & Technology, Assam
than 963 core peer-reviewed journals and a bibliographic
database (SCOPUS) in different disciplines from 21 overseas
21. Mizoram University, Mizoram
publishers and aggregators.
22. D. M. College of Science, Manipur)
The faculty members, scientists, research scholars and
23. Sikkim University, Gangtok
project assistants of the institutions covered under
24. College of Veterinary Science, Assam Agricultural
DeLCON are the primary beneficiaries.
University, Guwahati
25. Gauhati University, Assam
The DeLCON comprises currently the following 33 member
26. Manipur University, Imphal 27. College of Veterinary Science & Animal Husbandry
DBT Institutions
Central Agricultural University, Mizoram
1. National Brain Research Centre (NBRC), Manesar
28. Rajiv Gandhi University, Arunachal Pradesh
2. National Institute of Plant Genome Research (NIPGR) -
29. Nagaland University, Nagaland
30. North-Eastern Hill University, Shillong
3. National Institute of Immunology (NII) - New Delhi
31. St. Anthony's College, Meghalaya
4. National Centre for Cell Science (NCCS) - Pune
32. Tezpur University, Tezpur, Sonitpur, Assam
5. Institute of Life Sciences (ILS) – Bhubaneshwar
33. Sikkim State Council of Science and Technology,
6. Institute of Bioresources and Sustainable Development
The complete list of full-text resources (e-Journals) and
7. Centre for DNA Fingerprinting and Diagnostics (CDFD)
bibliographic databases, subscribed under the DeLCON
Consortium, is available from http://delcon.gov.in.
National Brain Research Centre
NATIONAL NEUROIMAGING FACILITY
The 3 Tesla Phillips whole body MRI scanner at our Facility is
National Neuroimaging facility, sponsored by the
equipped with state-of-the-art hardware, software and data
Department of Biotechnology, Govt. of India, came into
processing software required for each imaging modality.
existence in the year of 2006. The main purpose this
The facility is being used for performing structural,
National Facility to facilitate/support cutting edge brain
metabolic (multinuclear, e.g. proton and phosphorous) and
imaging research. The facility is equipped with four state-
functional MRI. In addition to understanding brain function
of-the-art equipments such as,
and clinical research, the center also is closely interacting
with leading imaging centers within the country and across
1. 3T Magnetic Resonance Imaging (MRI)Scanner
2. Electroencephalography (EEG)
Electroencephalography (EEG) is a test that measures
3. Evoked Response Potential Recording (ERP)
and records the electrical activity of the brain. Special
sensors are attached to the head and hooked by wires to
MAGNETIC RESONANCE IMAGING (MRI)
a computer. The computer records brain's electrical activity
MRI provides much greater contrast between the
on the screen or on paper as wavy lines. Certain conditions,
different soft tissues of the body compared to computed
such as epilepsy, dementia, consciousness and narcolepsy
tomography (CT), making it especially useful in neurological
(sleeping disorder) can be studied by EEG.
(brain), musculoskeletal, cardiovascular. Various imaging
modalities also play important role providing crucial
Evoked Response Potential Recording (ERP) is an
information which can aid to various diagnostic process.
electrical potential recorded from the nervous system of a
There are various imaging modalities, which are:
human or other animal following presentation of a stimulus.
Evoked potential amplitudes tend to be low, ranging from
1. MR Spectroscopy (MRS) which provides non-invasive
less than a microvolt to several microvolts
neurochemical level estimations and enables clinical
Clinical studies on patients with Alzheimer's Parkinson's
2. Functional MRI (fMRI) which, as the name suggests
and Autism as well as monitoring of aging in normal healthy
correlates functional (haemodynamics) activity with
brain is being performed extensively in this National Neuro
images of brain activation
imaging facility.
National Brain Research Centre
Translational Research:
TRANSLATIONAL & CLINICAL
attending, and movement disorders are an important cause
of attendance. Patients attending the OPD at Civil Hospital
Consultant Clinical Professor: Dr. V. S. Mehta
come from old Gurgaon township and the villages and
towns in the surrounding districts of Haryana, while some
Consultant Clinical Assistant Professor: Dr Kapil Agarwal
come from neighbouring states as Rajasthan, Uttarkhand,
Consultant Clinical Assistant Professor: Dr Rajnish Kumar
Delhi and Uttar Pradesh.
Clinical Neuropsychologist: Dr Preeti Singh
Patients requiring advanced specialist neurology in-patient
Clinic Assistant: Hanuman Singh and Pawan Kumar
care are referred to All-India Institute of Medical Sciences
(AIIMS), Institute of Postgraduate Medical Education
The unit is located at the Government General Hospital,
& Research – Rohtak, Institute of Human Behaviour &
Civil Lines, Gurgaon 122001.
Allied Sciences (IHBAS), or Vardhaman Medical College
(Safdarjung Hospital), New Delhi or to other tertiary
hospital as per the choice of the patient, if he so desires. As
part of the major plans for renovation of Civil Hospital, the
The following facilities are available to the patients of the
Neurology OPD rooms have been refurbished and space
unit through the hospital/clinics at concessional rates:
has been allotted for NBRC in the outpatient area, which
can accommodate other members of our team.
MRI system: Siemens Magnetom 1.5 Tesla scanner with
Outpatient case records in neurology are maintained from
various study protocols
the outset, aside from relevant entry into the patient OP
case sheets, which the patients keep in their possession. A
comprehensive Neurology case sheet has been formulated
and formatted by Distributed Information Centre of NBRC.
We are undertaking to prospectively enter all the medical
Neurophysiology: EEG, Evoked response, EMG.
data of new patients, to create computer database with
X-ray and Contrast imaging.
relevant patient data along with any planned imaging/
molecular/neurophysiological studies at the NBRC labs,
thus creating a well documented "clinical window" for our
Biochemistry, Microbiology, Haematology, Pathology &
research institute. In this effort to narrow the gap between
Basic Neuroscience and Applied Neuroscience, an ethics
committee protocol has been formulated jointly with the
Translational research aims to connect basic research
Government General Hospital/Government of Haryana.
to patient care: "From the Bench lab to the Bedside
The association of NBRC with Alzheimer's & Related
patient". The Clinical Research Unit of NBRC covers the full
Disorders Society of India (ARDSI) which has been going
spectrum of clinical neuroscience: neurology, neurosurgery,
on from 2005, has been further fostered. This interaction
neuropsychology, neuropsychiatry, behavioral therapy, and
promises to grow to the mutual benefit of both institutions
psychometry. The unit has a morning outpatient facility, at
concerned primarily with the common goal of the care
the Government General Hospital four days a week, each
of the elderly in its varied aspects. Besides medical and
of the consultant clinical faculty is available on one of the
neurological health conditions, one is exposed to the
designated days. The NBRC Unit has integrated well with
psychosocial and public health problems of the ageing
the Civil hospital medical team and there is an increasing
populace in their home environment.
number of referrals from other in-house departments
Further expansion of the electrophysiological facility is
and local hospitals. If a patient of the unit requires
underway, with procurement of 64-channel high density
indoor treatment or observation, then, with courtesy of
EEG/evoked potential response analysis, electrical
neuropsychiatrists and specialists of internal medicine of
dipole source mapping, Electromyography (EMG) and
the General Hospital, the patient is taken care of. The out-
Neurophysiological studies as Nerve Conduction velocity
patients facility is busy, and on some days attendance can
system and neurometry.
exceed forty patients.
For proper functioning and further clinical support, the Unit
The follow up by the patients is about 85%. Male to female
receives the fullest cooperation of the Ministry of Health -
ratio is almost equal. Paediatric group patient attendance is
Government of Haryana, and the Deputy Commissioner -
mainly for management of epileptic seizure and disorders
Gurgaon, as well as from the Civil Surgeon and the Principal
of the mentally challenged. There are also elderly patients
Medical Officer of the Hospital.
National Brain Research Centre
Meeting & Workshops
Prof. Ramamurthi Memorial Lecture
THE LATE DR. B. RAMAMURTHI
MEMORIAL LECTURE
The VIIIth late Dr. B. Ramamurthi Memorial Lecture was delivered by Prof. Vijayalakshmi Ravindranath, Chairperson, Centre
for Neuroscience Indian Institute of Science (IISc), Bengaluru on 8th February 2013, at the National Brain Research Centre in
Manesar. This series of lecture which were initiated in 2006 commemorates Professor Ramamurthi's immense contribution
role in setting up NBRC. Prof. Subrata Sinha, Director, NBRC, discussed Prof. Ramamurthi's contributions to Neuroscience
with emphasis on his role in the setting up of a centre devoted to research in Neuroscience. Prof. Ravindranath scientific
oration was entitled "The changing demography and challenge for Neuroscience".
National Brain Research Centre
International Collaborations
& Networking
multidisciplinary approach by bringing together scientists
working in different disciplines into the main stream of
neuroscience and brain research activity. The networking
Dr. Pankaj Seth has been awarded two grants from USA for
is possible by information sharing through electronic
collaborative research. The NIH-RO1 grant is in collaboration
network and identifying "Collaborating" centres for mutual
with Dr. Carlos Pardos, Johns Hopkins University, Baltimore,
interaction. Currently 48 centres throughout India are
USA. This NIH-RO1 grant proposes to study the "Role of CNS
networked to NBRC. The following institutions/universities
opportunistic infections in subsequent development of HIV
are member of our network activities
dementia". The NIH R21 grant is awarded in collaboration
with Prof Shilpa Buch, University of Nebraska Medical
List of Network Centres
Center, USA. This NIH-R21 grant proposes to study the
1. All India Institute of Medical Sciences (AIIMS), New
"Molecular Mechanisms & Therapy for Cocaine Abuse in
HIV Associated Neurocognitive Disorder (HAND).
2. Banaras Hindu University (BHU), Varanasi.
3. Bangur Institute of Neurology, Kolkata.
Dr. Nihar Jana and Dr. Nobuyuki Nukina (RIKEN Brain
4. Centre for Behavioural and Cognitive Sciences (CBCS),
Science Institute, Japan) have a grant together for studying.
University of Allahabad, Allahabad.
"Role of ubiquitin-proteasome system dysfunction in
5. Centre for Cellular & Molecular Biology (CCMB),
the pathogenesis of Huntington's disease." Dr. Jana
also has another grant in collaboration with Dr. Amit
Mishra (IIT, Jodhpur) and Dr. Koji Yamanaka (RIKEN Brain
6. Central Drug Research Institute (CDRI), Lucknow.
Science Institute, Japan) to study "Role of Ube3a in ALS
7. Centre for DNA Fingerprinting and Diagnostic,
8. Central Food and Technological Research Institute
(CFTRI), Mysore.
Prof. Prasun Roy and Prof. Peter Luijten, Utrecht Medical
9. Cochin University of Science and Technology, Cochin.
Centre, are working together on developing high-field
neuroimaging methodology which has been sponsored
10. Department of Biotechnology. New Delhi.
by Utrecht University Research Foundation and Philips
11. Delhi University, South Campus, Delhi.
12. Dr. A. L. Neurosurgical Centre, Chennai.
13. Indo American Hospital Brain and Spine Center, Kerala.
A neuroimaging project on imaging systems and networks
14. Institute of Cybernetics, Systems and Information
has beeninitiated by Prof. Prasun Roy and Prof. Alan Evans,
Technology, Kolkata.
Montreal Neurological Institute, McGill University.
15. International Centre for Genetic Engineering and
Biotechnology (ICGEB), New Delhi.
NETWORKING
16. Institute of Genomics and Integrative Biology (IGIB),
A major goal of NBRC is to network the existing
neuroscience groups/ institutions in the country and
17. Institute of Human Behaviour & Allied Sciences
promote multidisciplinary research in neuroscience. This
(IHBAS), Delhi.
is aimed to prevent unnecessary duplication of the work
18. Indian Institute of Information Technology (IIIT),
and facilities already existing. It also facilitates sharing of
expertise and available infrastructure for mutual benefit.
Networking also helps to bring together researchers from
19. Indian Institute of Technology (IIT), Mumbai.
varying backgrounds to pursue common objectives that
20. Indian Institute of Technology (IIT), Delhi.
may be beyond the capacity of an individual investigator,
group or institution. This is important because major
21. Indian Institute of Technology (IIT), Kanpur.
achievements in neuroscience are being made through a
22. Indian Institute of Science (IIS), Bangalore.
National Brain Research Centre
23. Indian Institute of Chemical Biology (IICB), Kolkata.
36. Nizam's Institute for Medical Sciences (NIMS),
24. Institute of Nuclear Medicine and Allied Sciences
(INMAS), New Delhi.
37. Rajiv Gandhi Centre for Biotechnology, Trivandrum.
25. Industrial Toxicology Research Centre (ITRC), Lucknow.
38. National Neuroscience Centre (NNC), Kolkata.
26. Indian Statistical Institute, Kolkata.
39. Sanjay Gandhi Post-Graduate Institute of Medical
27. International School of Photomics, Cochin.
Sciences (SGPGIMS), Lucknow.
28. Jagadguru Sri Shivarathreeshwara Medical College,
40. School of Information Technology, West Bengal
29. Jawaharlal Nehru University (JNU), New Delhi.
41. Shree Chitra Tirunal Institute for Medical Sciences and
30. Jawaharlal Nehru Centre for Advance Scientific
Research (JNCASR), Bangalore.
42. Sri Venkateswara Institute of Medical Sciences, Tirupati.
31. Jiwaji University, Gwalior.
43. Tata Institute of Fundamental Research (TIFR),
32. M.S. University of Baroda (Dept. of Microbiology and
Biotechnology Centre), Baroda.
44. University College of Medical Sciences (UCMS), Delhi.
33. National Centre for Biological Sciences (NCBS),
45. University of Hyderabad, Hyderabad.
46. University of Calcutta, Kolkata.
34. National Informatics Centre (Medical Informatics and
47. Vidyasagar Institute of Mental Health and
Telemedicine Division), (NIC) New Delhi.
Neuroscience (VIMHANS), New Delhi.
35. National Institute of Mental Health & Neuroscience
48. Vision Research Foundation, Chennai
National Brain Research Centre
Name of the Speaker
Title of the Lecture
Oculomotor Decision Making by Predictive April 16, 2012
The Smith-Kettlewell Eye Research Institute, San Deselection of Antagonist Rule in Supplementary
Francisco, California
Proteomics & Signal Transduction Pathway &
Institute of Bioinformatics Bangalore
Dr. Alapakkam Sampath
Optimal processing of photoreceptor signals is June 19, 2012
USC Keck School of Medicine
required to maximize
behavioral sensitivity near absolute visual
Role of inhibition in causing and correction of June 22, 2012
University of Freiburg
Parkinson's disease related brain dynamics
Windows to the Brain: Domains and Determinants July 2, 2012
Assistant Professor, Section of Sleep Medicine, of Sleep Apnea Induced Morbidity
Department of Pediatrics, The Knapp Center for
Biomedical Discovery, The University of Chicago
Medical Center, Chicago
Dr. Sharda Prasad Yadav
ranscription and splicing associated protein July 2, 2012
NonO/p54nrb augments rhodopsin expression
synergistically with NRL and CRX
Dr. Sachin Deshmukh
Objects, space, and memory: how the hippocampal July 23, 2012
Mind/Brain Institute Johns Hopkins University, cognitive map comes together
Professor Rosalia Mendez
Cell therapy in Neurological disorders.
September 17, 2012
Instituto de Biofisica Carlos Chagas, Rio de Janeiro,
and October 3, 2012
Department of Neurosciences Department of Neurodegenerative Disorders
Pathology University of California San Diego USA
Dr. Anindya Ghosh Roy
Maintenance and Repair of neural circuit
University of California, San Diego
Dr. Vikaas S. Sohal
Using optogenetics to study how dopamine November 6, 2012
Assistant Professor Department of Psychiatry modulates normal and pathological activity in the
University of California, San Francisco, USA
prefrontal cortex
Dr. Nixon Abraham
Role of synaptic inhibition in odor discrimination
November 27, 2012
University of Geneva
Prof. Iqbal Ahmad
Treating Neuronal Degeneration - From Within November 29, 2012
Professor of Ophthalmology &Visual Sciences And Without
Associate Dean, Academic affairs Director,
Postdoctoral Education & Research, University of
Nebraska Medical Center, Omaha, USA
National Brain Research Centre
Dr. Dipanjan Roy from Technical University Berlin Influence of cell type specificity, astrocytic December 3, 2012
glutamate uptake on representations in the
primary visual cortex
Protein misfolding and neurodegeneration December 5, 2012
Maiti University of California, Los Angeles
caused by amyloid deposition: role of molecular
Dr. Mahendra S Rao, Director Center for Using stem cells in translational medicine
December 17, 2012
Regenerative Medicine, National Institutes of
Health, Bethesda, USA
Dr. Kaveri Rajaraman
Listening to Bass Notes: How to Make Size Not December 20, 2012
Center for Ecological Sciences IISc, Bangalore
Prof. Vijaylakshmi Ravindranath
The changing demography and challenge for February 8, 2012
Chairperson Centre for Neurosceinece IISc, neuroscience
Dr. Debanjan Goswami, Stanford University, USA
Unique February 12, 2013
Postsynaptic SNARE Fusion Machinery
Prof. Tej Pandita
Role of MOF in DNA Damage Response and February 14, 2013
Department of Radiation Oncology, UT Beyond
Southwestern Medical Center, Texas USA
Dr. James Chelliah
Pathogenic SYNGAP1 haploinsufficiency impairs February 15, 2013
Scripps Research Institute, USA
cognitive development by disrupting the
maturation of dendritic spine synapses
Brain Networks of Anatomical Covariances
February 13, 2013
Montreal Neurological Institute McGill University
Dr. Bart Krekelberg
Neural Mechanisms of Perceptual Stability
February 13, 2013
Associate professor Rutgers University
Dr. Amitabha Majumder
The role of a self-sustaining amyloidogenic protein February 19, 2013
Stowers Institute, USA
in persistence of memory.
Dr. Abrar Qurashi
Non coding RNA-mediated neurodegeneration in March 4, 2013
Mount Sinai School of Medicine, USA
fragile X-associated tremor/ataxia syndrome
Imaging biomarkers in schizophrenia: promising March 5, 2013
Additional Professor of Psychiatry and an Adjunct leads from research at MBIAL
faculty of Clinical Neurosciences, and Head,
Multimodal Brain Image Analysis Laboratory
National Brain Research Centre
from diverse backgrounds including Bachelor's degree in
any branch related to Neurosciences, M.B.B.S., B.E., B. Tech.
Deemed University Status
or Psychology. NBRC recognizes that understanding brain
NBRC was awarded Deemed University status (de-novo
functions requires a fusion of knowledge from multiple
category) in 2002 under Section 3 of UGC Act, 1956 (3 of
1956) vide notification No.F.9-52/2001-U.3 dated 20th May,
2002 issued by Ministry of Human Resources Development,
Integrated Ph.D. Students are provided a fellowship of
Government of India. NBRC is the first Institute among the
5000/- per month for the first two years. From third year
Institutes of the Department of Biotechnology to attain this
onwards they are paid fellowship on par with Ph.D. students.
After completion of the Integrated Ph.D. programme, the
students will be given dual degree (M.Sc. and Ph.D.). NBRC
On completion of 5 years period from the time NBRC has
is one of the first Institutes in the country to develop an
been given de-novo deemed University status, a Committee
integrated multidisciplinary teaching programme in Life
(duly constituted by UGC) visited NBRC for reviewing the
‘Deemed to be University' status and recommended further
extension. The deemed university status has also been
NBRC offers certain benefits to its students in the form of
reviewed by an independent Committee constituted by
fellowships, hostel accommodation, transportation facility,
Ministry of HRD. The Committee gave an excellent report
medical reimbursement to its students.
and placed this University / Institute under "A" category.
Summer Training and Short-term Programmes
UGC desired to re-assess and review the deemed university
NBRC conducted Summer Training Programme for the
status and again a duly constituted Committee visited
Students through three National Science Academies viz: (1)
NBRC again and gave a very good report. The notification
Indian Academy of Science, Bangalore (2) Indian National
from Ministry of HRD is awaited.
Science Academy, New Delhi (3) National Academy of
Sciences, Allahabad. The summer training was for a
period of 8 weeks. The Trainees were provided with shared
accommodation in the Hostel of NBRC during their training
Ph.D. in Neuroscience
period. Summer trainees were encouraged to attend
NBRC has a Ph.D. Programme in Neuroscience to develop
seminars and journal clubs organized at the Institute.
trained manpower having a broad overview of different
aspects of Neuroscience.
The summer training projects give students an exposure
to Neuroscience and encourage them to consider it as a
NBRC inducts students for its Ph.D. programme from
future career option.
diverse backgrounds including Masters degree in any
branch related to Neurosciences, Psychology or M.B.B.S.,
NBRC celebrated its 9th Foundation Day on 16th December
B.E., or B.Tech. NBRC recognizes that understanding brain
2012. Six schools from Gurgaon / Manesar participated in
functions requires a fusion of knowledge from multiple
the open exhibition and quiz, held at NBRC in connection
with the Foundation Day celebrations. The events included
Lab visits and poster viewing by students, Lecture in the
Fellowship for Junior Research Fellows is 16,000/- per
Seminar Hall (Given by senior students) and Quiz.
month and for Senior Research Fellows it is 18,000/-
NBRC celebrated the National Science Day on 28th February,
Integrated-Ph.D. in Neuroscience
NBRC has an Integrated Ph.D. Programme in Neuroscience
On this occasion Integrated Ph.D. student, Post Doctoral
to develop trained manpower having a broad overview of
Fellow and other project employee of NBRC participated in
different aspects of Neuroscience.
a presentation at Kendriya Vidhayala, NSG, Manesar, Govt.
Senior Secondary School, Pachgaon and Amity University,
NBRC inducts students for its Integrated Ph.D. programme
Manesar, Gurgaon.
National Brain Research Centre
General & Academic
Administration – A Profile
GENERAL & ACADEMIC
Brain Imaging and Modeling Section, National Institute
ADMINISTRATION – A PROFILE
on Deafness and other Communication Disorders
The General Administration of the Institute consists of the
(NIDCD), National Institutes of Health, Bethesda, MD,
following major wings:
Implementation of Official Language
1. General Administration, headed by the Chief
Administrative Officer, who is responsible for
NBRC Administration has given due importance for the
overall Management of Establishment, Personnel &
implementation of Hindi as the Official Language at this
Administration Wing, Stores & Purchase Wing, Import
centre and has made full efforts to implement the use of
& Project Cell, Finance & Accounts Wing, Estate
Official Language in all the administrative jobs such as
Management & Engineering Maintenance Wing – Civil,
internal official meetings, interviews, debates, general
Electrical & Mechanical.
applications etc. NBRC Administration received a letter of
appreciation from the Ministry of Home Affairs, Regional
2. Academic Administration is headed by the Registrar,
Implementation Office, Ghaziabad towards implementation
who is responsible for the students' administration,
of Hindi in day to day official work during the year. The
project co-ordination, new students' admissions, course
Rajbhasha Sansthan, New Delhi awarded NBRC with
co-ordination etc. The officer is also responsible for the
a shield in recognition of its efforts made towards the
administration of DIC.
implementation of Hindi as the official language.
During the year under review, the Administration achieved
excellence in execution of following activities at NBRC:
RTI Act
The provisions of RTI Act are being followed at NBRC in
• The annual cultural festival of NBRC, ‘TANTRIKA 2012'
letter and in spirit. All RTI applications received during 2012-
was organized within the campus which included a
13 seeking information on various matters concerning
variety of cultural and sports events. Students, officers,
NBRC were provided the requisite information within the
and staff of NBRC participated in the event.
prescribed time limit.
• Provided necessary logistics in conducting international
and national conferences/seminars organized in the
campus as well outside of the campus.
NBRC has a distinct feature of giving equal opportunity to
• Made major imports from different countries in terms of
women. The Committees, constituted to do various work
equipments and other consumables with meticulous
of Administration, Academics and scientific activities, have
planning and adhered to a precise schedule.
women members in them which ensure fair participation
• The 9th Foundation Day of NBRC was held on 16th
and protection of women. There is a committee for
day of December, 2012. On this occasion, several
redressal of complaints relating to any sexual harassment of
programmes were organized within and outside the
women at NBRC and grievances, if any, from aggrieved girl
campus. The daylong celebrations included the poster
students/ women employees of NBRC. Any lady/ woman of
presentations on ongoing research activities of NBRC.
NBRC, among the Students/ Employees who is subjected
Students from various schools were invited to interact
to sexual harassment can approach any of the committee
with NBRC scientists and they visited the laboratories.
A quiz programme for students from local schools
was also organized on this occasion. On this august
occasion, Prof. Dr. Mahendra S. Rao, Director, Centre for
Reservations and concessions in Employment &
Regenerative Medicine, National Institutes of Healfh
Admissions of Students
(NIH), Bethesda, USA delivered the Foundation Day
NBRC follows reservations & concessions as the per rules
lecture to the students and scientific community at
of Government of India in employment, and in the matter
India International Centre, New Delhi.
of students' admissions, the provision of exemption as
• The Sadbhavana Diwas was observed in NBRC in
provided in Gazette Notification No. 5 dated 4th January,
the year 2012. The faculty, students and staff were
2007 is implemented.
administered a solemn pledge to work in harmony and
emotional oneness of all people regardless of region,
caste, religion or language.
The Institute has a Chief Vigilance Officer. As per the
• The process of recruiting Dr. Arpan Banerjee as Scientist
guidelines of DBT, one of the Officers of NBRC has been
was completed during 2012. Dr. Banerjee was in the
nominated as Chief Vigilance Officer of the Centre.
National Brain Research Centre
Institutional Governance Structure
& People at NBRC
Governing Council
Finance Committee
Scientific Advisory Committee
Building Committee
MEMBERS OF NBRC SOCIETY
MEMBERS OF THE GOVERNING COUNCIL
Prof. P. N. Tandon, (President)
Prof. K. VijayRaghavan, (Chairperson)
No. 1, Jagriti Enclave, Vikas Marg, New Delhi-
Secretary Department of Biotechnology, New Delhi
Dr. M.K. Bhan, Secretary
Prof. P.N. Tandon (Ex-officio)
Department of Biotechnology, New Delhi
No. 1, Jagriti Enclave, Vikas Marg, Delhi
Dr. T. Ramasami, Secretary
Prof. Upinder S. Bhalla, Scientist
Department of Science & Technology, New Delhi
National Centre for Biological Sciences (NCBS) Bangalore
Dr. V.M.Katoch, Director-General
Prof. Dinakar M. Salunke, Executive Director
Indian Council of Medical Research, New Delhi
Regional Centre for Biotechnology, Gurgaon
Dr. Sandip K. Basu JC Bose, Chair Professor
Dr. A.K. Agarwal (Ex-Officio)
National Institute of Science Commission & Information
Dean, Director, Professor & HOD, Maulana Azad Medical
Resources (NISCAIR) New Delhi
College, New Delhi
Dr. K. Vijayaraghavan, Director
Prof. G. Mehta, FNA, FRS
National Centre for Biological Sciences (NCBS) Bangalore,
Bhartia Chair School of Chemistry University of Hyderabad,
Prof. Samir K. Brahmachari, Director General
Dr. Chitra Sarkar
CSIR Institute of Genomics & Integrative Biology Delhi
Department of Pathology, All India Institute of Medical
Sciences (AIIMS), New Delhi
Ms.Vandana Srivastava, IDAS
JS & FA, Department of Biotechnology, New Delhi
8. Prof. Seyed E. Hasnain, Professor
Kusuma School of Biological Sciences, Indian Institute of
Dr. Gourie Devi, Director (Retd.)
Technology (IIT Delhi), New Delhi
Flat –9, Doctors Apartments, Vasundhara Enclave, Delhi
Ms. Anuradha Mitra, IDAS (Ex-officio)
10. Dr. L.M. Patnaik, CSA Department
Joint Secretary & Financial Advisor, Department of
Indian Institute of Science, Bangalore
Biotechnology, New Delhi
11. Prof. Kalluri Subba Rao, Prof. & Head of Biochemistry
Dr. V.M. Katoch, (Ex-Officio)
University of Hyderabad, School of Life Sciences
10. Director General, Indian Council for Medical Research, V.
Hyderabad , Andhra Pradesh
Ramalingaswamy Bhawan, New Delhi
12. Dr. T.S. Rao, Advisor
11. Dr. T. Ramasami, (Ex-Officio), Secretary
Department of Biotechnology, New Delhi
Department of Science & Technology (DST), New Delhi
13. Prof. Subrata Sinha, Director
Dr. T.S. Rao (Spl. Invitee), Advisor
National Brain Research Centre, Manesar, Haryana
12. Department of Biotechnology, New Delhi
13. Dr. Sanjeev Jain (Spl. Invitee)
Professor & HOD, Department of Psychiatry, NIMHANS,
14. Prof. Subrata Sinha (Ex-officio), Director
National Brain Research Centre, Gurgaon, Haryana
National Brain Research Centre
MEMBERS OF FINANCE COMMITTEE
Prof.K.VijayRaghavan Chairperson (Ex-officio)
Prof. Seyed E. Hasnain, Professor, Kusuma School of
Secretary, Department of Biotechnology, New Delhi
Biological Sciences, Indian Institute of Technology (IIT
Delhi), Hauz Khas, Delhi , Member
Ms. Anuradha Mitra, IDAS
(Ex-officio), Joint Secretary & Financial Advisor,
Prof. Subrata Sinha, Member (Ex-officio)
Department of Biotechnology, New Delhi
Director, National Brain Research Centre, Gurgaon,
Prof. Dinakar M. Salunke, Executive Director
Regional Centre for Biotechnology, Gurgaon, Haryana
Shri Rajesh Kumar Vyas, Non-Member Secretary (Ex-
Dr. K.P. Singh (UGC Nominee) Joint Secretary
Finance and Accounts Officer National Brain Research
University Grants Commission New Delhi
Centre Gurgaon, Haryana
MEMBERS OF SCIENTIFIC ADVISORY COMMITTEE
Prof. P.N. Tandon (Chairperson)
12. Dr. V. Rajshekhar
President, NBRC Society No. 1, Jagriti Enclave, Vikas Marg,
Department of Neurological Sciences, Christian Medical
College Hospital, CMC, Vellore
Prof. Upinder S. Bhalla, (Co-Chairperson)
13. Dr. Sanjeev Jain
Scientist, National Centre for Biological Sciences (NCBS),
Head of the Department, Department of Psychiatry,
NIMHANS, Bangalore
Prof. Vijayalakshmi Ravindranath, (Chairperson)
14. Prof. Sudipta Maiti
Centre for Neuroscience, Indian Institute of Sciences,
Deptt. of Chemical Sciences, TIFR, Mumbai
15. Prof. N.R. Jagannathan
Prof. Amitabha Chattopadhyay Scientist
Head of the Department of NMR and MRI Facility, All India
Centre for Cellular and Molecular Biology (CCMB),
Institute of Medical Sciences (AIIMS), New Delhi
16. Dr. Chitra Sarkar
Dr. Ayub Qadri, Scientist
Department of Pathology, All India Institute of Medical
National Institute of Immunology (NII), New Delhi
Sciences (AIIMS), New Delhi
17 Prof. Ajay Ray, Vice-Chancellor
Prof. Dinakar M. Salunke, Executive Director
Bengal Engineering & Science University, Shibpore,
Regional Centre for Biotechnology (RCB), Gurgaon
Howrah International Members
Prof. Siddhartha Roy, Director
Indian Institute of Chemical Biology (IICB), Kolkata
18. Prof. ARIEL RUIZ i ALTABA, Professor, Faculty of Medicine,
Prof. Jyotsna Dhawan, Scientist
University of Geneva, Department of Medicinal Genetics
Institute for Stem Cell Biology and Regenerative Medicine
Geneva, Switzerland
(inStem), NCBS, TIFR, Bangalore
19. Prof. Baroness Susan Greenfield, Professor, Department
of Pharmacology, Lincoln College, Oxford University, UK
National Centre for Biological Sciences, Bangalore
20. Prof. Thomas D. Albright, Professor, The Salk Institute for
Biological Studies, La Jolla, California, USA
10. Prof. Rohit Manchanda
21. Dr. Michael W. Weiner, MD, Director of the Center for
Biomedical Engineering Group, School of Biosciences
Imaging of Neurodegenerative Diseases, SFVAMC,
and Bioengineering, IITBombay, Mumbai
Professor of Radiology, Medicine, Psychiatry and
11. Prof. B.N. Mallick, Professor
Deptt. of Life Sciences, Jawaharlal Nehru University New
22. Dr. T.S. Rao, Member (Ex-officio) Adviser
Department of Biotechnology (DBT), New Delhi
National Brain Research Centre
MEMBERS OF BUILDING COMMITTEE
Dr. T.S. Rao, Advisor
Mr. M.K. Gupta, Engineer-In-Charge (Civil)
Department of Biotechnology, New Delhi
Inter University Accelerator Centre, JNU (New) Campus,
Dr. Sidhartha Satpathy, Professor
Department of Hospital Administration All India Institute
Prof. Subrata Sinha, Director
of Medical Sciences (AIIMS), New Delhi
National Brain Research Centre, Manesar, Haryana
Dr. Satish Gupta, Deputy Director
National Institute of Immunology New Delhi
MEMBERS OF ACADEMIC COUNCIL
Prof. Subrata Sinha (Chairman)
11. Dr. Ellora Sen
Director, National Brain Research Centre, Manesar,
National Brain Research Centre, Manesar, Haryana
12. Dr. Shiv Kumar Sharma
Prof. Nihar Ranjan Jana
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
13. Dr. Nandini C. Singh
Prof. Basabi Bhaumik
National Brain Research Centre, Manesar, Haryana
Department of Electrical Engineering, Indian Institute of
14. Dr. Soumya Iyengar
Technology, New Delhi
National Brain Research Centre, Manesar, Haryana
Prof. Pankaj Seth
15. Dr. Narender K. Dhingra
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
16. Dr. Yoganarasimha Doreswamy
Paras Hospitals, Gurgaon, Haryana
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
17. Prof. Neeraj Jain
National Brain Research Centre, Manesar, Haryana
Prof. K. Muralidhar, Head, Dept. of Zoology
University of Delhi, Delhi
18. Dr. Sourav Banerjee
National Brain Research Centre, Manesar, Haryana
Prof. Pravat K. Mandal
National Brain Research Centre, Manesar, Haryana
19. Dr. Sharba Bandyopadhyay
(Till 27-03-2013 A.N.), National Brain Research Centre,
National Brain Research Centre, Manesar, Haryana
20. Mr. K.V.S.Kameswara Rao
10. Dr. Ranjit K. Giri
National Brain Research Centre, Manesar, Haryana
21. National Brain Research Centre, Manesar, Haryana
National Brain Research Centre
MEMBERS OF BOARD OF STUDIES
Prof. Subrata Sinha, Director
11. Dr. Nandini C. Singh
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
Prof. Pankaj Seth
12. Dr. Soumya Iyengar
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
13. Dr. Narender K. Dhingra
Indian Institute of Sciences, Bangalore, Karnataka
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
14. Dr. Yoganarasimha Doreswamy
National Brain Research Centre, Manesar, Haryana
Prof. Rohit Manchanda
Indian Institute of Technology, Mumbai, Maharashtra
15. Prof. Neeraj Jain
National Brain Research Centre, Manesar, Haryana
Prof. Pravat K. Mandal
National Brain Research Centre, Manesar, Haryana
16. Prof. Nihar Ranjan Jana
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
17. Dr. Sourav Banerjee
National Brain Research Centre, Manesar, Haryana
Dr. Ranjit K. Giri
National Brain Research Centre, Manesar, Haryana
18. Dr. Sharba Bandyopadhyay
(Till 27-03-2013 A.N.), National Brain Research Centre,
National Brain Research Centre, Manesar, Haryana
10. Dr. Shiv Kumar Sharma
19. Mr. K.V.S.Kameswara Rao
National Brain Research Centre, Manesar, Haryana
National Brain Research Centre, Manesar, Haryana
Scientists
Prof. Subrata Sinha (Director)
Dr. Supriya Bhavnani
Prof. Prasun Kumar Roy
Prof. Neeraj Jain
Dr. Tora Mitra Ganguli (Till 30/04/12)
Dr. Nihar Ranjan Jana
Scientist (WOS - A)
Dr. Pravat Kumar Mandal
Dr. Sayali C. Ranade (DST Project) (Till 02/07/12-F.N.)
Post Doctoral Fellow (DST)
Dr. Narender K. Dhingra
Dr. Shiv Kumar Sharma
Dr. Ranjit Kumar Giri
Dr. Chetan Kumar Yadav
Dr. Nandini C. Singh
Dr. Soumya Iyengar
Dr. Shripad Arun Kondra (Till 18/05/12)
Dr. Kallol Dutta (RA III DBT Project) (Till 21/06/12)
Dr. Yoganarasimha Doreswamy
Dr. Arkadeb Dutta (RA II DBT Project) (Till 29/11/12)
Dr.Sanchari Sinha (Till 01/10/12)
Dr. Sourav Banerjee
Dr. Supriya Bhavnani (Till 20/11/12)
Dr. Sharba Bandyopadhyay
Dr. Rema Velayudhan
Dr. D.Subhashree (Till 17/09/12)
Dr. Vidhata Dixit (Till 04/04/12)
Prof. Partha Raghunathan
Dr. Amar Nath Maurya (Till 31/08/12)
National Brain Research Centre
Dr. T. Mrudula (RA I DBT Project) (Till 31/12/12)
R & D Engineer
Mr. Rajdeep Singh Rathore (Till 23/10/12)
Mr. Sukhvir Singh Pundir (DBT Project) (Till 20/09/12)
Ms. Tejaswini Adikane (Till 30/04/12)
Mr. Joshi Jitesh Narendra
Ms. T. A.Sumathi (Contingent Grant) (Till 20/09/12)
Junior R&D Engineer
Mr. Tanmay Nath (Till 31/08/12)
Mr. Karthik Vyawahare (Till 25/05/2012-F.N.)
Mr. Simranjot Singh (Till 27/11/12)
Mr. Arnab Chakrabarti (Till 11/05/12)
Ms. Shruti Sukumar Kothari
Mr. Sagnik Datta (Till 27/02/13)
Technical Officer (Project)
Ms.Rashi Midha (DBT Project)
Mr. Ayan Sengupta
Ms. T.Ammaponnu @Sumathi
Mr. Rahul V. V. (Till 27/06/12)
Mr. Ashwat Nagarajan (Till 23/04/12)
Senior Research Officer (Computer Engineering)
Ms. Aparna Pandey (Till 14/03/13)
Mr. V. P. Subramanyam Rallabandi
Mr. Arkoprovo Paul
Mr. Hemant Kumar Srivastava
Mr. Mukesh Kumar Vaidya
Senior R&D Engineer (Project)
Mr. Bharath H.N.
Dr. Thounaojam Menaka Chanu
Dr. Gouri Shanker Patil
Dr. Sumiti Saharan
Dr. Neelanjana Roy
Project Associate (DeLCON)
Dr. Arpita Chatterjee
Ms. Namrata Gupta
National Brain Research Centre
Dr. Chinmoyee Maharana (Till 08-10-12 A.N.)
22. Mr. I Mohd Ariff (Till 02-08-2012)
23. Mr.Sandeep Kumar
Mr. Niranjan Ashok Kambi
24. Mr.Vaibhav Tyagi
Ms. Neha Sehgal (Till 27-02-13 A.N.)
25. Mr.Sourish Ghosh
Mohd. Hisham P.M.
26. Mr.Bharat Prajapati
Ms. Radhika Rajan
27. Ms.Mahar Fatima
Ms. Shilpa Mishra Shukla
28. Mr.Atesh Koul
Mr. Subhadip Paul
29. Mr.Vasav J.Arora
Ms.Rupali Srivastava
30. Mr.Brijesh Kumar Singh
10. Mr. Kaushik Pramod Sharma
31. Mr. John Thomas
11. Ms. Neha Bhutani
32. Mr.Arghya Dutta Choudhury (Till 14-05-2012)
12. Ms. K.M.Sharika
33. Mr.Kautuk Kamboj
13. Dr. Sudheendra Rao NR
34. Mr. Biswaranjan Sahoo
14. Mr. Rahul Chaudhary
35. Mr. Indrajith R. Nair
15. Mr. Pankaj S Ghate
36. Ms. Mandrita Barua
16. Mr. Deepak Kr Kaushik
37. Mr. Muneshwar
17. Mr. Deobrat Dixit
38. Ms. Pushpa Kumari
39. Ms. Shalini Swaroop
19. Mr. Arshed Nazmi
40. Mr. Shashi Shekhar Kumar
20. Mr. Apoorv Sharma
41. Mr. Touseef Ahmad Sheikh
21. Ms. Manju Tewari
42. Mr. Tushar Arora
National Brain Research Centre
INTEGRATED Ph.D. STUDENTS
Ms. G.Swetha Kameshwari
21. Ms. Manju Tewari
Mr.Priyabrata Halder
Mr. Sadashib Ghosh
Ms. Megha Maheshwari
Ms.Rekha S.Varrier
Ms.Chitra Mohinder Singh Singhal
Mr. Pavan Kumar R.
Ms.Utkarsha A. Singh
Mr. Atul Gopal PA
Ms.Pooja Parishar
Mr.Apurva Agrawal
Ms. Suhela Kapoor
Ms. Guncha Bhasin
Ms. Sarika Cherodath
Mr. Abhishek Kumar Verma
Mr. Chandan Kumar Kharga
Ms. Ruchi Ghildiyal
Mr. Hriday Shanker Pandey
Ms. Piyushi Gupta
Ms. Avantika Mathur
Ms. Shankhamala Sen
20. Mr. Apoorv Sharma
Mr. Vipendra Kumar
National Brain Research Centre
Ms.Kanchan Bisht (Till 08-06-12)
23. Mr. Anshu Khandelwal
Ms. Ananya Samanta (Till 31-08-12)
Mr. Namit Bharija (Till 28-09-12)
Mr.Diptendu Mukherjee
Mr. Kuldeep Tripathi
Mr.Dwaipayan Adhya (Till 17-08-12)
Mr. Nikhil Anto P.
Ms.Anya Chakraborty (Till 30-07-12)
Ms. Avipsa Mohanty (Till 24-04-12)
Ms. Snigdha Kundu (Roy) (Till 12-04-12)
Mr.G.Naga Rajesh (Till 28-02-13)
Ms. Ankita Srivastava (Till 14-12-12)
Mr. Nikhil Ahuja (Till 13-07-12)
Mr. Rajiv Ramaswamy
Ms. Sarbani Samaddar
Ms.Panghki Medhi (Till 05-06-12)
Ms. Keerthi Ramanujan
Ms. Rinki Saha (Till 04-06-12)
Mr. Kaushik Kumar Deka (Till 07-09-12)
Ms. Sriparna Mukherjee
Ms. Saba Parween (Till 31-08-12)
Ms. Bhuvaneswari Ganesan
Mr. Bandhan Mukherjee
Mr. Hariom Sharma
Mr. Abhinaba Ghosh (Till 18-12-12)
Ms. Ananya Chakraborty
Mr. Aniruddha Das (Till 04-01-13)
Mr. Rajarshi Mukherjee
Ms. Teesta Naskar
Ms. Rabia Khatoon
Mr. Tanveer Verma (Till 09-07-12)
Mr. Prajwal Pradeep Thakre
Mr. Arkoprovo Paul (Till 31-07-12)
Ms. Sriya Bhattacharya
Ms. Jyothirmayi Vadlamudi
22. Mr. Kiran Kundu
Mr. Ashwat Nagarajan (Till 11-10-12)
National Brain Research Centre
(OTHER STAFF) - TECHNICAL STAFF
15. Mr. Ankit Sharma
Mr. Sanjeev K. Choudhary
16. Mr. Sanjeev Bhardwaj
17. Mr. Yunis Khan
Mr. Mahender Kumar Singh
Mr. Jitender Ahlawat
19. Mr. S. Suresh Kumar (till 16.01.2013)
Mr. Arvind Singh Pundir
20. Mr. Durgalal Meena
Dr. Inderjeet Yadav
21. Mr. Irshad Alam
Mr. Kanhaiya Lal Kumawat
22. Mr. P. Manish
Mr. Kedar Singh Bajetha
23. Mr. Dil Bahadur Karki
10. Mr. Shankar Dutt Joshi
11. Mr. Sumit Kumar Sinha Mahapatra
25. Mr. Manish Kumar
12. Mr. D. Narender
26. Mr. Hari Shankar
13. Mr. Sanjay Kumar
27. Mr. Mahendra Singh
14. Mr. Mithlesh Kumar Singh
28. Mr. Sanjay Kumar Singh
Mr. K.V.S. Kameswara Rao
18. Mr. Satish Kumar
Mr. N. Subramanian
DIC Project Staff
Mr. Rajesh Kumar Vyas
Mr. Santosh Kumar Choudhary
Mr. Debashish Bhattacharjee
Mr. R. Ganesh Gurumoorthy
Mr. Sunil Kumar Dwivedi
Construction Project Staff
Mr. Shailender Singh
Mr. Sanjay Kumar Gupta
Mr. Anil Kumar Yadav
10. Mr. Shiv Kumar
Mr. Bhupender Singh
11. Mr. Rajbir Singh
Mr. Subhashji Roy
Contractual Staff
13. Mr. Ajay Kumar Dehariaya
Dr. Kuldeep Sharma
14. Mr. Himanshu Mal
Dr. Aloknath Gupta
15. Mr. Rakesh Kumar Yadav
Mr. Mukesh Chauhan
16. Mr. Surender Kumar
Mr. Mukesh Kumar Pandey
17. Mr. Bhupender Pal Sharma
Ms. Shweta Mishra
National Brain Research Centre
Source: http://www.nbrc.ac.in/download/annualreport/AR_2012-13.pdf
10.2.2010 Amtsblatt RICHTLINIE 2010/11/EU DER KOMMISSION vom 9. Februar 2010 zur Änderung der Richtlinie 98/8/EG des Europäischen Parlaments und des Rates zwecks Aufnahme des Wirkstoffs Warfarin in Anhang I (Text von Bedeutung für den EWR) DIE EUROPÄISCHE KOMMISSION — gen werden, dass als Rodentizide verwendete Biozid-Pro
Available online at Anomalous self-experience and childhood trauma in Elisabeth Hauga,⁎, Merete Øiea,b, Ole A. Andreassen c, Unni Bratlien a, Barnaby Nelson d, Monica Aas c, Paul Møller e, Ingrid Melle c aDivision of Mental Health, Innlandet Hospital Trust, Ottestad, Norway bDepartment of Psychology, University of Oslo, Oslo, Norway cNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, Division of Mental Health and Addiction, University of Oslo, and Oslo
