National Brain Research Center

Haryana, India

National Brain Research Center

Haryana, India
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Ranade S.C.,National Brain Research Center
The British journal of nutrition | Year: 2012

Maternal malnutrition affects every aspect of fetal development. The present study asked the question whether a low-protein diet of the mother could result in motor deficits in the offspring. Further, to examine whether cerebellar pathology was correlated with motor deficits, several parameters of the postnatal development of the cerebellum were assayed. This is especially important because the development of the cerebellum is unique in that the time scale of development is protracted compared with that of the cortex or hippocampus. The most important result of the study is that animals born to protein-deficient mothers showed significant delays in motor development as assessed by rotarod and gait analysis. These animals also showed reduced cell proliferation and reduced thickness in the external granular layer. There was a reduction in the number of calbindin-positive Purkinje cells (PC) and granular cells in the internal granular layer. However, glial fibrillary acidic protein-positive population including Bergmann glia remained unaffected. We therefore conclude that the development of the granular cell layer and the PC is specifically prone to the effects of protein malnutrition potentially due to their protracted developmental period from approximately embryonic day 11 to 13 until about the third postnatal week.

Jana N.R.,National Brain Research Center
Neural Plasticity | Year: 2012

Angelman syndrome (AS) is a neuroDevelopmental disorDer characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by Deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging eviDence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-depenDent synaptic plasticity. A number of animal models for AS have been generated to unDerstand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into unDerstanding the disease biology for potential therapeutic intervention. © Copyright 2012 Nihar Ranjan Jana.

Chand P.,National Brain Research Center | Jain N.,National Brain Research Center
Journal of Neuroscience | Year: 2015

Brains of adult monkeys with chronic lesions of dorsal columns of spinal cord at cervical levels undergo large-scale reorganization. Reorganization results in expansion of intact chin inputs, which reactivate neurons in the deafferented hand representation in the primary somatosensory cortex (area 3b), ventroposterior nucleus of the thalamus and cuneate nucleus of the brainstem. A likely contributing mechanism for this large-scale plasticity is sprouting of axons across the hand–face border. Here we determined whether such sprouting takes place in area 3b. We first determined the extent of intrinsic corticocortical connectivity between the hand and the face representations in normal area 3b. Small amounts of neuroanatomical tracers were injected in these representations close to the electrophysiologically determined hand–face border. Locations of the labeled neurons were mapped with respect to the detailed electrophysiological somatotopicmapsand histologically determined hand–face border revealed in sections of the flattened cortex stained for myelin. Results show that intracortical projections across the hand–face border are few. In monkeys with chronic unilateral lesions of the dorsal columns and expanded chin representation, connections across the hand–face border were not different compared with normal monkeys. Thalamocortical connections from the hand and face representations in the ventroposterior nucleus to area 3b also remained unaltered after injury. The results show that sprouting of intrinsic connections in area 3b or the thalamocortical inputs does not contribute to large-scale cortical plasticity. © 2015 the authors.

Cherodath S.,National Brain Research Center | Singh N.C.,National Brain Research Center
Brain and Language | Year: 2015

Children in bilingual societies often simultaneously acquire reading skills in distinct writing systems that vary in consistency of sound-letter mapping or orthographic depth. To investigate its effect on cortical reading networks in children, we performed functional imaging on 34 simultaneous Hindi-English biliterate children as they read word and nonword stimuli. In contrast to Hindi which is consistent and relies on phonological assembly for both stimuli, English is inconsistent which necessitates lexical retrieval for words, but phonological assembly for nonwords. While children recruited a shared reading network for both languages, factorial analysis revealed stimulus effects (word/nonword) in bilateral frontal, parietal and left angular regions. Subsequent analyses showed that the stimulus effect was significant in English, which has a deep orthography, in comparison to Hindi, which is transparent. Our results provide novel evidence that orthographic depth shapes cortical reading processes during development. © 2015 Elsevier Inc.

Mandal P.K.,National Brain Research Center
European Journal of Radiology | Year: 2012

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging modality for metabolite detection in different parts of the body (e.g. brain, liver, prostate, breast, kidney, skeletal muscle, and heart) for normal person as well as in various disorders. It aids in providing valuable information for both diagnosis as well as therapeutic monitoring. Though there has been tremendous progress in MRS signal processing techniques for the quantitation of neurometabolites, variability in the absolute quantitation of metabolites persists due to various experimental conditions. In this article, we present in-depth discussion on 1H MRS data processing and quantitation using different software packages both in frequency (e.g. LCModel) and time domain (e.g. jMRUI). We have included comparative analysis of precision and accuracy of MRS data processing using LCModel and jMRUI (AMARES). Special emphasis has been provided for the handling of macromolecules and lipid in LCModel and jMRUI methods. The author also suggests certain points to be noted while opting for above software packages. © 2011 Elsevier Ireland Ltd. All rights reserved.

Schifilliti D.,Messina University | Mandal P.K.,National Brain Research Center
Anaesthesia | Year: 2010

With longevity, postoperative cognitive decline in the elderly has emerged as a major health concern for which several factors have been implicated, one of the most recent being the role of anaesthetics. Interactions of anaesthetic agents and different targets have been studied at the molecular, cellular and structural anatomical levels. Recent in vitro nuclear magnetic resonance spectroscopy studies have shown that several anaesthetics act on the oligomerisation of amyloid β peptide. Uncontrolled production, oligomerisation and deposition of amyloid β peptide, with subsequent development of amyloid plaques, are fundamental steps in the generation of Alzheimer's disease. Amyloid β peptide is naturally present in the central nervous system, and is found at higher tissue concentrations in the elderly. We argue that administering certain general anaesthetics to elderly patients may worsen amyloid β peptide oligomerisation and deposition and thus increase the risk of developing postoperative cognitive dysfunction. The aim of this review is to highlight the clinical aspects of postoperative cognitive dysfunction and to find plausible links between possible anaesthetic effects and the molecular pathological mechanism of Alzheimer's disease. It is hoped that our hypothesis will stimulate further enquiry, especially triggering research into elucidating those anaesthetics that may be more suitable when cognitive dysfunction is a particular concern. © 2010 The Association of Anaesthetists of Great Britain and Ireland.

Jana N.R.,National Brain Research Center
Neurochemistry International | Year: 2012

Protein homeostasis is fundamental in normal cellular function and cell survival. The ubiquitin-proteasome system (UPS) plays a central role in maintaining the protein homeostasis network through selective elimination of misfolded and damaged proteins. Impaired function of UPS is implicated in normal aging process and also in several age-related neurodegenerative disorders that are characterized by increased accumulation oxidatively modified proteins and protein aggregates. Growing literature also indicate the potential role of various ubiquitin protein ligases in the regulation of aging process by enhancing the degradation of either central lifespan regulators or abnormally folded and damaged proteins. This review mainly focuses on our current understanding of the importance of UPS function in the regulation of normal aging process. © 2012 Elsevier Ltd. All rights reserved.

Rao C.,National Brain Research Center | Singh N.C.,National Brain Research Center
Brain and Language | Year: 2015

Neurocognitive processing of orthographic visuospatial complexity was examined through fMRI-based overt naming (n=16) of phonologically transparent, high and low frequency Hindi/Devanagari words that were visually simple or complex. Participants' overt behavior was modestly influenced by visuospatial complexity (accuracy: main effect p = 01, complexity×frequency interaction p<.07), while neuroimaging data revealed a robust effect of complexity (main effect FWE p<10-4, complexity×frequency interaction FWE p<7×10-8). Interaction-based RoIs showed higher BOLD response in the VWFA to complex and left posterior temporal cortex to simple words, with greater right lingual de-activation to complex than simple words. Subtractions confirmed additional recruitment of VWFA, right frontal, inferior orbitofrontal, mid-temporal pole and left cerebellum by visuospatially complex over simple words. Finally, low frequency words activated bilateral occipital and putamen areas, left IPL, SPL, IFG and VWFA, suggesting that effortful phonological processing in alphasyllabic Hindi/Devanagari requires neural resources specialized for both visuospatially simple and complex orthographies. © 2014 Elsevier Inc.

Saharan S.,National Brain Research Center | Mandal P.K.,National Brain Research Center
Journal of Alzheimer's Disease | Year: 2014

With millions of older individuals presently suffering from Alzheimer's disease (AD) worldwide, AD is an unduly common form of dementia that exacts a heavy toll on affected individuals and their families. One of the emerging causative factors associated with AD pathology is oxidative stress. This AD-related increase in oxidative stress has been attributed to decreased levels of the brain antioxidant, glutathione (GSH). In this article, we review the role of GSH in AD from a pathological as well as a diagnostic point of view. We recapitulate the literature that has assessed the role of GSH in AD onset and progression. We discuss the various methodologies through which alterations in GSH levels might be monitored, and highlight the yet uncharted potential of assaying GSH levels in vivo with magnetic resonance spectroscopy in AD therapeutics and prognostics. Finally, the present manuscript integrates findings from various studies to elucidate the possible molecular mechanisms through which disruptions in GSH homeostasis may contribute to AD pathology. © 2014 IOS Press and the authors. All rights reserved.

National Brain Research Center and All India Institute of Medical Sciences | Date: 2014-05-10

The present invention relates to cell specific therapeutic modality by using a region of the PLAP Promoter. The invention further relates to specific expression of therapeutically PLAP useful sequences for specific transcriptional activation of this gene. The invention also relates to the PLAP region which may be used alone or in combination with other regions like enhancer sequences that augment cell or tumour specific gene expression.

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