Dataset Information

Exercise Reduces H3K9me3 and Regulates Brain Derived Neurotrophic Factor and GABRA2 in an Age Dependent Manner.

ABSTRACT: Exercise improves cognition in the aging brain and is a key regulator of neuronal plasticity genes such as BDNF. However, the mechanism by which exercise modifies gene expression continues to be explored. The repressive histone modification H3K9me3 has been shown to impair cognition, reduce synaptic density and decrease BDNF in aged but not young mice. Treatment with ETP69, a selective inhibitor of H3K9me3's catalyzing enzyme (SUV39H1), restores synapses, BDNF and cognitive performance. GABA receptor expression, which modulates BDNF secretion, is also modulated by exercise and H3K9me3. In this study, we examined if exercise and ETP69 regulated neuronal plasticity genes by reducing H3K9me3 at their promoter regions. We further determined the effect of age on H3K9me3 promoter binding and neuronal plasticity gene expression. Exercise and ETP69 decreased H3K9me3 at BDNF promoter VI in aged mice, corresponding with an increase in BDNF VI expression with ETP69. Exercise increased GABRA2 in aged mice while increasing BDNF 1 in young mice, and both exercise and ETP69 reduced GABRA2 in young mice. Overall, H3K9me3 repression at BDNF and GABA receptor promoters decreased with age. Our findings suggest that exercise and SUV39H1 inhibition differentially modulate BDNF and GABRA2 expression in an age dependent manner.

SUBMITTER: Ionescu-Tucker A

PROVIDER: S-EPMC8712855 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exercise Reduces H3K9me3 and Regulates Brain Derived Neurotrophic Factor and GABRA2 in an Age Dependent Manner.

Ionescu-Tucker Andra A Butler Christopher W CW Berchtold Nicole C NC Matheos Dina P DP Wood Marcelo A MA Cotman Carl W CW

Frontiers in aging neuroscience 20211214

Exercise improves cognition in the aging brain and is a key regulator of neuronal plasticity genes such as BDNF. However, the mechanism by which exercise modifies gene expression continues to be explored. The repressive histone modification H3K9me3 has been shown to impair cognition, reduce synaptic density and decrease BDNF in aged but not young mice. Treatment with ETP69, a selective inhibitor of H3K9me3's catalyzing enzyme (SUV39H1), restores synapses, BDNF and cognitive performance. GABA rec ...[more]

PMID: 34970138

Similar Datasets

Project description:Many chronic trigeminal pain conditions, such as migraine or temporo-mandibular disorders, are associated with inflammation within peripheral endings of trigeminal ganglion (TG) sensory neurons. A critical role in mechanisms of neuroinflammation is attributed to proinflammatory cytokines, such as interleukin-1? and tumor necrosis factor-? (TNF?) that also contribute to mechanisms of persistent neuropathic pain resulting from nerve injury. However, the mechanisms of cytokine-mediated synaptic plasticity and nociceptor sensitization are not completely understood. In the present study, we examined the effects of TNF? on neuronal expression of brain-derived neurotrophic factor (BDNF), whose role in synaptic plasticity and sensitization of nociceptive pathways is well documented. We show that 4- and 24-h treatment with TNF? increases BDNF mRNA and protein, respectively, in neuron-enriched dissociated cultures of rat TG. TNF? increases the phosphorylated form of the cyclic AMP-responsive element binding protein (CREB), a transcription factor involved in regulation of BDNF expression in neurons, and activates transcription of BDNF exon IV (former exon III) and, to a lesser extent, exon VI (former exon IV), but not exon I. TNF?-mediated increase in BDNF expression is accompanied by increase in calcitonin gene-related peptide (CGRP), which is consistent with previously published studies, and indicates that both peptides are similarly regulated in TG neurons by inflammatory mediators. The effect of TNF? on BDNF expression is dependent on sodium influx through TTX-sensitive channels and on p38-mitogen-activated protein kinase. Moreover, electrical stimulation and forskolin, known to increase intracellular cAMP, potentiate the TNF?-mediated upregulation of BDNF expression. This study provides new evidence for a direct action of proinflammatory cytokines on TG primary sensory neurons, and reveals a mechanism through which TNF? stimulates de novo synthesis of BDNF in these neurons. Thus, TNF? should be considered in mechanisms of BDNF-dependent neuronal plasticity.

Dataset Information

Exercise Reduces H3K9me3 and Regulates Brain Derived Neurotrophic Factor and GABRA2 in an Age Dependent Manner.

Publications

Exercise Reduces H3K9me3 and Regulates Brain Derived Neurotrophic Factor and GABRA2 in an Age Dependent Manner.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets