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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-NFB axis regulates resistance to TNF induced apoptosis (ii) Ras/NFB 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 NFB. 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/NFB inhibitor Guggulsterone via to induce death.
Caspase 9 activation. While SANT1 decreased Gli1 activity, Guggulsterone inhibited Ras and NFB 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 NFB 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 NFB 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 NFB activity, and inhibition of NFB 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- NFB 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 /NFB 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-NFB 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-NFB 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 /NFB 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 National Brain Research Centre 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 &
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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)
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21. Shashank Tandon, Niranjan Kambi, Hisham Mohammed 2. D K Kaushik, and A Basu (2013) A friend in need
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may not be a friend indeed: role of microglia in motor cortex of adult rats following long-term spinal neurodegenerative diseases. CNS & Neurological
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Disorders-Drug Targets (in press)
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rhodopsin in a mouse model of inherited retinal 4. Iyengar S (2012): Development of the Human Auditory
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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 /NFB 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

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