SOCIAL DEFEAT INDUCES CHANGES IN HISTONE ACETYLATION AND EXPRESSION OF HISTONE MODIFYING ENZYMES IN THE VENTRAL HIPPOCAMPUS, PREFRONTAL CORTEX, AND DORSAL RAPHE NUCLEUS
SOCIAL DEFEAT INDUCES CHANGES IN HISTONE ACETYLATION AND EXPRESSION OF HISTONE MODIFYING ENZYMES IN THE VENTRAL HIPPOCAMPUS, PREFRONTAL CORTEX, AND DORSAL RAPHE NUCLEUS
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DOI：
10.1016/j.neuroscience.2013.01.024
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发表时间：
2014-04-04
期刊：
影响因子：
3.3
通讯作者：
Abel, T.
中科院分区：
文献类型：
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作者：
Kenworthy, C. A.;Sengupta, A.;Abel, T.
长期暴露于压力与许多精神疾病有关，但对压力反应或对慢性压力的恢复力的表观遗传机制知之甚少。我们研究了慢性社会失败应激大鼠7个不同脑区的组蛋白乙酰化：背侧海马（dHPC）、腹侧海马（vHPC）、内侧前额叶皮质（mPFC）、基底外侧杏仁核（BLA）、蓝斑（LC）、室旁丘脑（PVT）和中缝背核（DR）。这种压力模式是独特的，因为它允许大鼠以积极应对机制的形式表现出弹性。我们发现，在恢复力较低的大鼠的DR核中，H3 K9/14（H3 K9/14 ac）的乙酰化和H4 K5，8，12，16（H4 K5，8，12，16 ac）的大量乙酰化增加。与非应激对照组相比，弹性较低的大鼠mPFC中的H3 K18乙酰化（H3 K18 ac）水平也有所增加。在vHPC中，与非应激对照大鼠相比，弹性较差的大鼠中H3 K18 ac和H4 K12（H4 K12 ac）增加。此外，与对照组相比，弹性和非弹性大鼠中的H4 K8乙酰化（H4 K8 ac）水平降低。我们使用定量实时聚合酶链反应（PCR）评估了vHPC和mPFC中组蛋白修饰酶的表达，发现了许多靶点表达的变化。这些变化包括vHPC中Sirt 1和Sirt 2的变化以及mPFC中Kat 5的变化。总体而言，这些结果表明，组蛋白乙酰化和组蛋白修饰酶在这些地区的表达变化与社会失败rats.This文章的一部分，题为：表观遗传学在脑功能的特殊问题的行为反应的压力。(C)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Chronic exposure to stress is associated with a number of psychiatric disorders, but little is known about the epigenetic mechanisms that underlie the stress response or resilience to chronic stress. We investigated histone acetylation in seven different brain regions of rats exposed to chronic social defeat stress: the dorsal hippocampus (dHPC), ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), basolateral amygdala (BLA), locus coeruleus (LC), paraventricular thalamus (PVT), and dorsal raphe (DR) nucleus. This stress paradigm was unique in that it allowed rats to display resilience in the form of an active coping mechanism. We found that there was an increase in acetylation of H3K9/14 (H3K9/14ac) and bulk acetylation of H4K5,8,12,16 (H4K5,8,12,16ac) in the DR nucleus of rats that were less resilient. Less resilient rats also displayed increased levels of H3K18 acetylation (H3K18ac) in the mPFC when compared to non-stressed controls. In the vHPC, there was an increase in H3K18ac and H4K12 (H4K12ac) in rats that were less resilient when compared to non-stressed control rats. In addition, there was a decrease in levels of H4K8 acetylation (H4K8ac) in both resilient and non-resilient rats as compared to controls. We assessed expression of histone modifying enzymes in the vHPC and the mPFC using quantitative real-time polymerase chain reaction (PCR) and found changes in expression of a number of targets. These included changes in Sirt1 and Sirt2 in the vHPC and changes in Kat5 in the mPFC. Overall, these results suggest that changes in histone acetylation and expression of histone modifying enzymes in these regions correlate with the behavioral response to stress in socially defeated rats.This article is part of a Special Issue entitled: Epigenetics in Brain Function. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.