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Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation.

机译:运动通过参与表观遗传调控机制影响脑源性神经营养因子可塑性。

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We have evaluated the possibility that the action of voluntary exercise on the regulation of brain-derived neurotrophic factor (BDNF), a molecule important for rat hippocampal learning, could involve mechanisms of epigenetic regulation. We focused the studies on the Bdnf promoter IV, as this region is highly responsive to neuronal activity. We have found that exercise stimulates DNA demethylation in Bdnf promoter IV, and elevates levels of activated methyl-CpG-binding protein 2, as well as BDNF mRNA and protein in the rat hippocampus. Chromatin immunoprecipitation assay showed that exercise increases acetylation of histone H3, and protein assessment showed that exercise elevates the ratio of acetylated :total for histone H3 but had no effects on histone H4 levels. Exercise also reduces levels of the histone deacetylase 5 mRNA and protein implicated in the regulation of the Bdnf gene [N.M. Tsankova et al. (2006)Nat. Neurosci., 9, 519-525], but did not affect histone deacetylase 9. Exercise elevated the phosphorylated forms of calcium/calmodulin-dependent protein kinase II and cAMP response element binding protein, implicated in the pathways by which neural activity influences the epigenetic regulation of gene transcription, i.e. Bdnf. These results showing the influence of exercise on the remodeling of chromatin containing the Bdnf gene emphasize the importance of exercise on the control of gene transcription in the context of brain function and plasticity. Reported information about the impact of a behavior, inherently involved in the daily human routine, on the epigenome opens exciting new directions and therapeutic opportunities in the war against neurological and psychiatric disorders.
机译:我们评估了自愿运动对调节脑源性神经营养因子(BDNF)(对大鼠海马学习重要的分子)的作用可能涉及表观遗传调控的可能性。我们将研究重点放在Bdnf启动子IV上,因为该区域对神经元活动高度敏感。我们发现,运动会刺激Bdnf启动子IV中的DNA去甲基化,并提高大鼠海马中活化的甲基CpG结合蛋白2以及BDNF mRNA和蛋白的水平。染色质免疫沉淀试验表明,运动可增加组蛋白H3的乙酰化程度,蛋白质评估显示,运动可提高组蛋白H3的乙酰化比例:总比例,但对组蛋白H4的水平无影响。运动还降低了与Bdnf基因调控有关的组蛋白脱乙酰基酶5 mRNA和蛋白的水平。 Tsankova等。 (2006年) Neurosci。,9,519-525],但不影响组蛋白脱乙酰基酶9。运动提高了钙/钙调蛋白依赖性蛋白激酶II和cAMP反应元件结合蛋白的磷酸化形式,这与神经活动影响表观遗传的途径有关基因转录的调节,即Bdnf。这些结果表明锻炼对含有Bdnf基因的染色质重塑的影响,强调了锻炼在脑功能和可塑性范围内控制基因转录的重要性。关于人类日常行为固有影响的行为对表观基因组的影响的报道信息为抗击神经和精神疾病提供了令人兴奋的新方向和治疗机会。

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