Modulation of Neurogenesis by Targeting Epigenetic Enzymes Using Small Molecules: An Overview

Swaminathan, Amrutha; Kumar, Manoj; Sinha, Sarmistha H.; Schneider‐Anthony, Anne; Boutillier, Anne‐Laurence; Kundu, Tapas K.

doi:10.1021/cn500117a

Cited by 15 publications

(7 citation statements)

References 172 publications

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“…Different from gene-based therapy, epigenetics regulate gene expression but cause no changes in the DNA sequence, minimizing the risk of gene mutation. Molecules targeting at epigenetic modifications include histone methylation, DNA methylation (Swaminathan et al, 2014 ) as well as non-coding RNA. The Ramous lab recently reported a new-discovered long non-coding RNA.…”

Section: Discussion and Future Directionmentioning

confidence: 99%

Electrical Stimulation Elicits Neural Stem Cells Activation: New Perspectives in CNS Repair

Huang

Li²,

Chen

et al. 2015

Front. Hum. Neurosci.

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Researchers are enthusiastically concerned about neural stem cell (NSC) therapy in a wide array of diseases, including stroke, neurodegenerative disease, spinal cord injury, and depression. Although enormous evidences have demonstrated that neurobehavioral improvement may benefit from NSC-supporting regeneration in animal models, approaches to endogenous and transplanted NSCs are blocked by hurdles of migration, proliferation, maturation, and integration of NSCs. Electrical stimulation (ES) may be a selective non-drug approach for mobilizing NSCs in the central nervous system. This technique is suitable for clinical application, because it is well established and its potential complications are manageable. Here, we provide a comprehensive review of the emerging positive role of different electrical cues in regulating NSC biology in vitro and in vivo, as well as biomaterial-based and chemical stimulation of NSCs. In the future, ES combined with stem cell therapy or other cues probably becomes an approach for promoting brain repair.

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Section: Discussion and Future Directionmentioning

confidence: 99%

Electrical Stimulation Elicits Neural Stem Cells Activation: New Perspectives in CNS Repair

Huang

Li²,

Chen

et al. 2015

Front. Hum. Neurosci.

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“…Epigenetic modifications, such as histone and DNA methylation and acetylation, contribute to both neurodevelopment directly and the influence of environment on neurodevelopment ( Kofink et al, 2013 ; Szyf, 2013 ). Gene expression can be dynamically changed by histone acetylation through histone acetyltransferase and histone deacetylase ( Kalkhoven, 2004 ; Lilja et al, 2013 ; Valor et al, 2013 ; Sheikh, 2014 ; Swaminathan et al, 2014 ). Acetylation of lysine by histone H3 alters transcription and has been implicated in ethanol-induced alterations to synaptic plasticity that contribute to anxiety and alcohol self-administration ( Pascual et al, 2012 ; Moonat et al, 2013 ; Krishnan et al, 2014 ; Sakharkar et al, 2014 ).…”

Section: Adolescent Alcohol-induced Epigenetic Alterations In Genmentioning

confidence: 99%

Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

et al. 2016

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Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence.

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“…The dynamic regulation of histone acetylation by the interaction of histone deacetylases (HDACs) and histone acetyltransferases (HATs), binding protein of cyclic adenosine monophosphate response element binding (CREB) protein (CBP) and p300, represents important epigenetic processes that are involved in brain development and functions throughout life (Kalkhoven 2004; Lilja et al 2013; Valor et al 2013; Sheikh 2014; Swaminathan et al 2014). Histone H3 acetylation of specific lysine residues within given gene promoters regulates transcription and contributes to alcohol-induced changes in the expression of synaptic plasticity associated genes and results in psychopathology, such as anxiety and alcohol use (Pascual et al 2012; Moonat et al 2013; Sakharkar et al 2014a; Krishnan et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Histone acetylation also regulates adult neurogenesis in preclinical models (Leone et al 2014; Swaminathan et al 2014; Yoo et al 2015). Recently, we observed the ability of HDAC inhibitors, such as trichostatin A (TSA), to reverse adolescent intermittent ethanol (AIE) exposure-induced anxiety-like and alcohol drinking behaviors, as well as reverse the deficits in histone H3-K9&14 acetylation of the BDNF gene in the amygdala during adulthood (Pandey et al 2015).…”

Section: Introductionmentioning

confidence: 99%

A role for histone acetylation mechanisms in adolescent alcohol exposure-induced deficits in hippocampal brain-derived neurotrophic factor expression and neurogenesis markers in adulthood

et al. 2016

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Binge drinking during adolescence is a risk factor for neuropsychiatric disorders that can develop later in life. Histone acetylation is an important epigenetic mechanism that contributes to neurodevelopment. We investigated the effects of adolescent intermittent ethanol (AIE) exposure, as opposed to normal saline (AIS) exposure, on histone acetylation-mediated regulation of brainderived neurotrophic factor (BDNF) expression and developmental stages of neurogenesis (proliferating and immature neurons) in the hippocampus in adulthood. AIE exposure increased whole hippocampal histone deacetylase (HDAC) activity and decreased binding protein of cyclic adenosine monophosphate response element binding protein (CBP) and histone H3-K9 acetylation levels in the CA1, CA2, and CA3 regions of the hippocampus. BDNF protein and exon IV mRNA levels in the CA1 and CA3 regions of the hippocampus of AIE exposed adult rats were decreased as compared to AIS exposed adult rats. AIE induced anxiety-like behaviors and deficits in histone H3 acetylation at BDNF exon IV promoter in the hippocampus during adulthood, which were reversed by treatment with the HDAC inhibitor, trichostatin A (TSA). Similarly, neurogenesis was inhibited by AIE in adulthood as demonstrated by the decrease in Ki-67 and doublecortin (DCX)-positive cells in the dentate gyrus, which was normalized by TSA treatment. These results indicate that AIE exposure increases HDACs and decreases CBP levels that may be associated with a decrease in histone H3 acetylation in the hippocampus. These epigenetic changes potentially decrease BDNF expression and inhibit neurogenesis in the hippocampus that may be involved in AIE-induced behavioral abnormalities, including anxiety, in adulthood.

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Modulation of Neurogenesis by Targeting Epigenetic Enzymes Using Small Molecules: An Overview

Cited by 15 publications

References 172 publications

Electrical Stimulation Elicits Neural Stem Cells Activation: New Perspectives in CNS Repair

Electrical Stimulation Elicits Neural Stem Cells Activation: New Perspectives in CNS Repair

Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

A role for histone acetylation mechanisms in adolescent alcohol exposure-induced deficits in hippocampal brain-derived neurotrophic factor expression and neurogenesis markers in adulthood

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