Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation.
Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation.
复制标题
DOI：
10.1111/j.1460-9568.2010.07508.x
复制
发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Fan G
中科院分区：
文献类型：
--
作者：
Gomez-Pinilla F;Zhuang Y;Feng J;Ying Z;Fan G
我们已经评估了自愿运动对脑源性神经营养因子（BDNF）（一种对大鼠海马学习很重要的分子）的调节作用可能涉及表观遗传调节机制的可能性。我们将研究集中在BDNF启动子IV上，因为该区域对神经元活动高度敏感。我们已经发现，运动刺激BDNF启动子IV的DNA去甲基化，并提高激活的甲基-CpG结合蛋白2的水平，以及大鼠海马中BDNF mRNA和蛋白质的水平。染色质免疫沉淀分析表明，运动增加组蛋白H3的乙酰化，和蛋白质评估表明，运动提高组蛋白H3的乙酰化：总的比率，但对组蛋白H4水平没有影响。运动还降低了组蛋白去乙酰化酶5 mRNA和与Bdnf基因调控有关的蛋白质的水平[N.M.国家神经科学，9，519-525]，但不影响组蛋白脱乙酰酶9。运动升高了钙/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，这与神经活动影响基因转录的表观遗传调控（即BDNF）的途径有关。这些结果表明，运动对含有BDNF基因的染色质重塑的影响，强调了运动在脑功能和可塑性的背景下对基因转录控制的重要性。关于行为影响的报道信息，内在地参与了人类的日常生活，在表观基因组上开辟了令人兴奋的新方向和治疗机会，在对抗神经和精神疾病的战争中。
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. 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.
登录
查看更多内容
DOI：
10.1111/j.1460-9568.2008.06524.x
发表时间：
2008-12
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Gomez-Pinilla F;Vaynman S;Ying Z
通讯作者：
Ying Z
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping
DOI：
10.1523/jneurosci.1786-08.2008
发表时间：
2008-10-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lubin FD;Roth TL;Sweatt JD
通讯作者：
Sweatt JD
影响因子：
3.3
作者：
Griesbach, GS;Hovda, DA;Gomez-Pinilla, F
通讯作者：
Gomez-Pinilla, F
影响因子：
3.4
作者：
Vaynman, S;Ying, Z;Gomez-Pinilla, F
通讯作者：
Gomez-Pinilla, F