Browsing by Author "Sweta Srivas"

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Aging of the Brain
(Elsevier, 2019) Sweta Srivas; Mahendra K. Thakur
Anatomical, biochemical and physiological characteristics of the brain change with age. Some of these alterations are common whereas others occur differentially in brain regions of different individuals. These changes further affect different brain processes such as cognition leading to several neurological as well as neuropsychiatric pathologies. Cognition is regulated by different life experiences which help in maintaining cognitive reserve. Genetic and epigenetic factors also play an important role in regulation of cognition through modulating the expression of memory-linked genes during aging. Recent advancements in understanding the aging brain suggest challenges and potential therapeutic interventions for successful aging. In this regard, studies have highlighted the role of healthy life-style and noninvasive brain stimulation to prevent cognitive impairments, neurological and psychiatric disorders during aging of the brain. © 2019 Elsevier Inc. All rights reserved.
Aging of the brain
(Elsevier, 2019) Sweta Srivas; Mahendra K. Thakur
Anatomical, biochemical and physiological characteristics of the brain change with age. Some of these alterations are common whereas others occur differentially in brain regions of different individuals. These changes further affect different brain processes such as cognition leading to several neurological as well as neuropsychiatric pathologies. Cognition is regulated by different life experiences which help in maintaining cognitive reserve. Genetic and epigenetic factors also play an important role in regulation of cognition through modulating the expression of memory-linked genes during aging. Recent advancements in understanding the aging brain suggest challenges and potential therapeutic interventions for successful aging. In this regard, studies have highlighted the role of healthy life-style and noninvasive brain stimulation to prevent cognitive impairments, neurological and psychiatric disorders during aging of the brain. © 2020 Elsevier Inc. All rights reserved.
Cognitive Changes with Aging
(Springer, 2019) Meghraj Singh Baghel; Padmanabh Singh; Sweta Srivas; Mahendra Kumar Thakur
Aging is a natural phenomenon associated with accumulation of several changes resulting in increased risk to various diseases. About 8.5% of total world population is aged 65 years and above, and around 40% of this elderly population is suffering with mild cognitive impairment. Such age associated cognitive impairment occurs in different domains such as attention, perception, reasoning, decision making, execution, speech and language. The impairment depends on vulnerability of different brain regions and their associated dysfunctions with advancing age. The cognitive impairment results in abnormal behavior which ultimately influences the quality of life and becomes a serious concern for the family and society. Therefore, it is important to understand the underlying basis of cognitive changes during normal aging and pathological conditions. Such knowledge will help to develop strategies for the improvement of quality of life, particularly for elderly population. In this review, the authors discuss the age associated changes in different cognitive functions and elucidate the accompanying genetic and environmental factors. Altogether, it seems possible to maintain the cognitive functions intact during aging by following a balanced life style, proper exercise and enriched environment. © 2017, The National Academy of Sciences, India.
Correction to: Epigenetic regulation of neuronal immediate early genes is associated with decline in their expression and memory consolidation in scopolamine-induced amnesic mice (Molecular Neurobiology, (2017), 54, 7, (5107-5119), 10.1007/s12035-016-0047-4)
(Humana Press Inc., 2019) Sweta Srivas; Mahendra K. Thakur
The original article inadvertently had a mistake in Fig. 3a, b. The authors regret to these errors. Now the correct images are hereby published. These corrections do not affect the content and conclusion of the manuscript. The authors apologize for any inconvenience caused to readers. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Epigenetic regulation of memory-therapeutic potential for disorders
(Bentham Science Publishers B.V., 2017) Padmanabh Singh; Sweta Srivas; M.K. Thakur
Background: Memory is a vital function which declines in different physiological and pathological conditions such as aging and neurodegenerative diseases. Research in the past has reported that memory formation and consolidation require the precise expression of synaptic plasticity genes. However, little is known about the regulation of these genes. Epigenetic modification is now a well established mechanism that regulates synaptic plasticity genes and neuronal functions including memory. Therefore, we have reviewed the epigenetic regulation of memory and its therapeutic potential for memory dysfunction during aging and neurological disorders. Method: Research reports and online contents relevant to epigenetic regulation of memory during physiological and pathological conditions have been compiled and discussed. Results: Epigenetic modifications include mainly DNA methylation and hydroxymethylation, histone acetylation and methylation which involve chromatin modifying enzymes. These epigenetic marks change during memory formation and impairment due to dementia, aging and neurodegeneration. As the epigenetic modifications are reversible, they can be modulated by enzyme inhibitors leading to the recovery of memory. Conclusion: Epigenetic modifications could be exploited as a potential therapeutic target to recover memory disorders during aging and pathological conditions. © 2017 Bentham Science Publishers.
Epigenetic regulation of neuronal immediate early genes is associated with decline in their expression and memory consolidation in scopolamine-induced amnesic mice
(Humana Press Inc., 2017) Sweta Srivas; Mahendra K. Thakur
Recently, we reported a correlation of scopolamine mediated decline in memory consolidation with increase in the expression of DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in the mouse hippocampus. Memory consolidation is a protein synthesis-dependent process which involves the expression of synaptic plasticity genes, particularly neuronal immediate early genes (IEGs). However, the mechanism of regulation of these genes during decline in memory is poorly understood. Therefore, we have studied the epigenetic regulation of expression of neuronal IEGs in scopolamine-induced amnesic mice. Scopolamine significantly impaired memory consolidation as tested by radial arm maze, and the expression of neuronal IEGs was downregulated in the hippocampus as revealed by qRT-PCR and Western blotting. Further, methylated DNA immunoprecipitation (MeDIP) analysis showed increase in DNA methylation, while chromatin immunoprecipitation (ChIP) revealed decrease in H3K9/14 acetylation at the promoter of neuronal IEGs. Taken together, the present study shows that increased DNA methylation and decreased histone acetylation at the promoter of neuronal IEGs are associated with decline in their expression and memory consolidation during scopolamine-induced amnesia. These findings suggest that the epigenetic regulation through altered DNA methylation and histone acetylation might be explored further to develop potential therapeutic interventions for amnesia. © 2016, Springer Science+Business Media New York.
Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment
(Blackwell Publishing Ltd, 2015) Padmanabh Singh; Arpita Konar; Ashish Kumar; Sweta Srivas; Mahendra K. Thakur
The amnesic potential of scopolamine is well manifested through synaptic plasticity gene expression changes and behavioral paradigms of memory impairment. However, the underlying mechanism remains obscure and consequently ideal therapeutic target is lacking. In this context, chromatin-modifying enzymes, which regulate memory gene expression changes, deserve major attention. Therefore, we analyzed the expression of chromatin-modifying enzymes and recovery potential of enzyme modulators in scopolamine-induced amnesia. Scopolamine administration drastically up-regulated DNA methyltransferases (DNMT1) and HDAC2 expression while CREB-binding protein (CBP), DNMT3a and DNMT3b remained unaffected. HDAC inhibitor sodium butyrate and DNMT inhibitor Aza-2′deoxycytidine recovered scopolamine-impaired hippocampal-dependent memory consolidation with concomitant increase in the expression of synaptic plasticity genes Brain-derived neurotrophic factor (BDNF) and Arc and level of histone H3K9 and H3K14 acetylation and decrease in DNA methylation level. Sodium butyrate showed more pronounced effect than Aza-2′deoxycytidine and their co-administration did not exhibit synergistic effect on gene expression. Taken together, we showed for the first time that scopolamine-induced up-regulation of chromatin-modifying enzymes, HDAC2 and DNMT1, leads to gene expression changes and consequent decline in memory consolidation. Our findings on the action of scopolamine as an epigenetic modulator can pave a path for ideal therapeutic targets. © 2015 International Society for Neurochemistry.
Pyrus pashia fruit extract and its major phytometabolite chrysin prevent hippocampal apoptosis and memory impairment in PTZ-kindled mice
(Taylor and Francis Ltd., 2024) Priyanka Sharma; Amita Kumari; Padmanabh Singh; Sweta Srivas; Mahendra K. Thakur; Siva Hemalatha
Objectives: Epilepsy is a chronic neurological condition with recurrent seizures. One-third of epilepsy patients experience unacceptable side effects from antiepileptic drugs. Pyrus pashia is a deciduous tree from southern Asia. Ethnomedicinally, Malakand tribes use its fruits for epilepsy treatment. Our prior research demonstrated the anticonvulsive properties of ethanolic extract of Pyrus pashia (EPP) and its bioactive compound chrysin in acute seizure tests. This study aims to investigate the impact of EPP and chrysin on cognitive impairment in a PTZ-induced kindling mice model of epilepsy. Methods: Swiss albino male mice were equally divided into four groups. The first group received 0.5% carboxy methyl cellulose dissolved in normal saline while the other three groups were pre-treated with Diazepam (DZP) (1 mg/kg, i.p.), EPP (200 mg/kg, p.o.) and chrysin (5 mg/kg, p.o.). After 30 min, all groups were administered PTZ (35 mg/kg, i.p.) and evaluated for seizure severity, cognitive function, and neuronal apoptosis. Western blot analysis was conducted to analyze the expressions of apoptosis biomarkers and memory-related genes, including cAMP response element-binding protein (CREB) and Brain Derived Neurotrophic Factor (BDNF). Results: The therapeutic effects of EPP and Chrysin were comparable to DZP in terms of reducing seizure severity, but unlike DZP, they prevented PTZ-induced memory impairment in experimental animals. Additionally, they increased the levels of BDNF and CREB while reducing apoptotic biomarkers in the hippocampus of experimental animals. Conclusions: Based on the leads offered by this study EPP and its major bioactive constituent, could be developed as the treatment option for epilepsy. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Transcriptional co-repressor SIN3A silencing rescues decline in memory consolidation during scopolamine-induced amnesia
(Blackwell Publishing Ltd, 2018) Sweta Srivas; Mahendra K. Thakur
Epigenetic modifications through methylation of DNA and acetylation of histones modulate neuronal gene expression and regulate long-term memory. Earlier we demonstrated that scopolamine-induced decrease in memory consolidation is correlated with enhanced expression of hippocampal DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in mice. DNMT1 and HDAC2 act together by recruiting a co-repressor complex and deacetylating the chromatin. The catalytic activity of HDACs is mainly dependent on its incorporation into multiprotein co-repressor complexes, among which SIN3A-HDAC2 co-repressor is widely studied to regulate synaptic plasticity. However, the involvement of co-repressor complex in regulating memory loss or amnesia is unexplored. This study examines the role of co-repressor SIN3A in scopolamine-induced amnesia through epigenetic changes in the hippocampus. Scopolamine treatment remarkably enhanced hippocampal SIN3A expression in mice. To prevent such increase in SIN3A expression, we used hippocampal infusion of SIN3A-siRNA and assessed the effect of SIN3A silencing on scopolamine-induced amnesia. Silencing of SIN3A in amnesic mice reduced the binding of HDAC2 at neuronal immediate early genes (IEGs) promoter, but did not change the expression of HDAC2. Furthermore, it increased acetylation of H3K9 and H3K14 at neuronal IEGs (Arc, Egr1, Homer1 and Narp) promoter, prevented scopolamine-induced down-regulation of IEGs and improved consolidation of memory during novel object recognition task. These findings together suggest that SIN3A has a critical role in regulation of synaptic plasticity and might act as a potential therapeutic target to rescue memory decline during amnesia and other neuropsychiatric pathologies. (Figure presented.). © 2018 International Society for Neurochemistry