Epigenetic regulation of BDNF gene in response to stress.
Epigenetic regulation of BDNF gene in response to stress.
复制标题
DOI：
10.4306/pi.2010.7.4.251
复制
发表时间：
2010-12
影响因子：
2.7
通讯作者：
Yamawaki S
中科院分区：
文献类型：
--
作者：
Fuchikami M;Yamamoto S;Morinobu S;Takei S;Yamawaki S
由突触形态和功能变化引起的神经元可塑性在学习、记忆和应激适应中起着重要作用。这表明，这些塑料变化是由于在大脑中的基因表达的变化编排。分子生物学的最新进展提供了证据表明，表观遗传机制，如DNA甲基化和组蛋白修饰，对哺乳动物大脑中的基因转录至关重要。我们的研究小组最近研究了组蛋白乙酰化在脑源性神经营养因子（BDNF）基因的启动子参与应激诱导的BDNF减少，以及在恐惧条件诱导的增强BDNF，在大鼠海马。应激研究的结果表明，单制动应力显着降低总，外显子I，和外显子IV BDNF mRNA的水平，也显着降低组蛋白H3的乙酰化水平，但不是H4，在外显子I，IV和VI的启动子。恐惧条件反射研究的结果表明，足电击应激显着增加了总的，外显子I，和外显子IV的BDNF mRNA的水平，显着增加组蛋白H3和H4的乙酰化水平，在外显子I和IV的启动子，其次是增强冻结恐惧上下文曝光。这些发现表明，大鼠海马体中脑源性神经营养因子转录响应压力刺激的变化至少部分受到组蛋白乙酰化状态的调节。
Neuronal plasticity induced by changes in synaptic morphology and function is well known to play a pivotal role in leaning and memory as well as adaptation to stress. It is suggested that these plastic changes are due to orchestration of alterations in gene expression in the brain. Recent advances in molecular biology have provided evidence that epigenetic mechanisms, such as DNA methylation and histone modification, are crucial to gene transcription in the mammalian brain. Our research group has recently investigated the involvement of histone actylation at the promoter of the brain-derived neurotrophic factor (BDNF) gene in stress-induced reduction in BDNF, as well as in fear conditioning-induced enhancement of BDNF, in the rat hippocampus. The results of the stress study demonstrated that single-immobilization stress significantly reduced the levels of total, exon I, and exon IV BDNF mRNA, and also significantly reduced acetylation levels of histone H3, but not H4, at the promoter of exons I, IV, and VI. The results of the fear conditioning study showed that footshock stress significantly increased the levels of total, exon I, and exon IV BDNF mRNA, with significantly increased acetylation levels of both histone H3 and H4, at the promoter of exons I and IV, followed by enhanced freezing to fear-context exposure. These findings suggest that changes in BDNF transcription in the rat hippocampus in response to stressful stimuli are, at least in part, regulated by histone acetylation status.
登录
查看更多内容
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：
5.3
作者：
Liu, IYC;Lyons, WE;Thompson, RF
通讯作者：
Thompson, RF
影响因子：
2.7
作者：
Miller, Courtney A.;Campbell, Susan L.;Sweatt, J. David
通讯作者：
Sweatt, J. David
影响因子：
5.3
作者：
Tsankova, NM;Kumar, A;Nestler, EJ
通讯作者：
Nestler, EJ
影响因子：
5.3
作者：
SMITH, MA;MAKINO, S;POST, RM
通讯作者：
POST, RM