Genomic and epigenomic responses to chronic stress involve miRNA-mediated programming.
Genomic and epigenomic responses to chronic stress involve miRNA-mediated programming.
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对慢性应激的基因组和表观基因组反应涉及 miRNA 介导的编程。
DOI：
10.1371/journal.pone.0029441
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Metz GA
中科院分区：
文献类型：
--
作者：
Babenko O;Golubov A;Ilnytskyy Y;Kovalchuk I;Metz GA
压力对运动系统功能有重要影响，并已被证明会损害运动表现。我们假设应激诱导的运动障碍是由于大脑特异性的miRNA和蛋白质编码基因表达的变化。在这里，我们显示了一个因果关系之间的联系，压力引起的运动障碍和相关的遗传和表观遗传反应在相关的中央运动区的大鼠模型。暴露于两周的轻度束缚应激改变了小脑中39个基因和9个miRNA的表达。与持续的行为障碍一致，基因和miRNA表达的一些变化对从压力中恢复具有抗性。有趣的是，应激上调了小脑中Adipoq和催乳素受体mRNA的表达。应激还改变了海马和前额皮质中Prlr、miR-186和miR-709的表达。此外，我们的研究结果表明，miR-186靶向基因Eps 15。此外，我们发现EphrinB 3和GabaA 4受体的年龄依赖性增加。这些数据表明，即使是轻微的应激也会导致涉及运动系统中miRNA表达和相关基因靶标的大量基因组和表观基因组变化。这些发现表明，miRNA调控的基因表达在应激反应和相关的神经功能中起着重要作用。
Stress represents a critical influence on motor system function and has been shown to impair movement performance. We hypothesized that stress-induced motor impairments are due to brain-specific changes in miRNA and protein-encoding gene expression. Here we show a causal link between stress-induced motor impairment and associated genetic and epigenetic responses in relevant central motor areas in a rat model. Exposure to two weeks of mild restraint stress altered the expression of 39 genes and nine miRNAs in the cerebellum. In line with persistent behavioural impairments, some changes in gene and miRNA expression were resistant to recovery from stress. Interestingly, stress up-regulated the expression of Adipoq and prolactin receptor mRNAs in the cerebellum. Stress also altered the expression of Prlr, miR-186, and miR-709 in hippocampus and prefrontal cortex. In addition, our findings demonstrate that miR-186 targets the gene Eps15. Furthermore, we found an age-dependent increase in EphrinB3 and GabaA4 receptors. These data show that even mild stress results in substantial genomic and epigenomic changes involving miRNA expression and associated gene targets in the motor system. These findings suggest a central role of miRNA-regulated gene expression in the stress response and in associated neurological function.
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影响因子：
3.1
作者：
Ioshikhes, Ilya;Roy, Sashwati;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
影响因子：
2.2
作者：
Collins, Ann L.;Ma, Deqiong;Whitehead, Patrice L.;Martin, Eden R.;Wright, Harry H.;Abramson, Ruth K.;Hussman, John P.;Haines, Jonathan L.;Cuccaro, Michael L.;Gilbert, John R.;Pericak-Vance, Margaret A.
通讯作者：
Pericak-Vance, Margaret A.
影响因子：
5.3
作者：
Colvis, CM;Pollock, JD;Nestler, EJ
通讯作者：
Nestler, EJ
DOI：
10.1073/pnas.0403382101
发表时间：
2004-07-13
影响因子：
11.1
作者：
Hug, C;Wang, J;Lodish, HF
通讯作者：
Lodish, HF
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.