Epigenetics of Social Defeat

项目摘要/摘要 组蛋白乙酰化和去乙酰化是表观遗传状态，可以产生 同时激活或沉默特定基因。这些翻译后版本 已经证明，这些过程发生在大脑中，并影响基因的表达。我们的 初步研究表明，在总体程度上存在基本差异 在对新奇事物反应不同的大鼠中，H3K14和H2B的乙酰化，而不是H4的乙酰化。 事实上，高反应大鼠(HR)表现出更高水平的H3K14和H3K14乙酰化水平 与低反应大鼠(LR)比较。有趣的是，长期的社会失败， 这是一种已建立的抑郁症动物模型，诱导了不同的乙酰化 H_3K_(14)和H_2B在HR和LR大鼠体内。社会挫败降低了乙酰化水平 H_3K_(14)和H_2B在HR大鼠中的表达，在LR大鼠中增加。然而，社会挫败 降低H4乙酰化水平，不依赖于HR和LR大鼠。由于人力资源和 LR大鼠表现出不同的情绪反应，其中HR大鼠更容易 类似抑郁症的现象，我们假设为 H3K14和H3B对新颖性反应的个体差异和对 慢性应激诱发的精神病态反应的个体差异。

Project Summary/Abstract Histone acetylation and deacetylation are epigenetic states that can produce simultaneously activation or silencing of specific genes. These post-translational processes have been shown to occur in the brain and to affect gene expression. Our preliminary studies show that there exist basal differences in the overall degree of acetylation of H3K14 and H2b, but not H4, in rats that differ in response to novelty. Indeed, the high responders rats (HR) exhibit higher levels of acetylation of H3K14 and H2b when compared to low responders rats (LR). Interestingly, chronic social defeat, which is an established animal model of depression, induces a differential acetylation of H3K14 and H2b in HR and LR rats. Social defeat decreases the acetylation levels on H3K14 and H2b in HR rats and increases it in the LR rats. Social defeat however decreased the level of acetylation of H4 independently of HR and LR rats. Since HR and LR rats exhibit different emotional responses, with the HR rats more prone to depression-like phenomena, we hypothesize that the epigenetic states described for the H3K14 and H2b contribute to individual differences in response to novelty and to individual differences in response to chronic stress-induced psychopathology.