Altered gene expression of histone deacetylases in mood disorder patients
Altered gene expression of histone deacetylases in mood disorder patients
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DOI：
10.1016/j.jpsychires.2009.08.015
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发表时间：
2010-04-01
影响因子：
4.8
通讯作者：
Watanabe, Yoshifumi
中科院分区：
文献类型：
--
作者：
Hobara, Teruyuki;Uchida, Shusaku;Watanabe, Yoshifumi
染色质重塑，如组蛋白乙酰化的变化已被认为在情绪障碍的病理生理学和治疗中发挥重要作用。在本研究中，我们调查组蛋白去乙酰化酶（HDAC）基因的表达是否在心境障碍患者中改变。采用实时荧光定量PCR技术检测了11种HDAC（HDAC 1 -11）在抑郁和缓解期的重性抑郁障碍（MDD）和双相情感障碍（BPD）患者以及BPD患者一级亲属外周血白色细胞中的mRNA水平。此外，我们研究了抗抑郁药和情绪稳定剂对小鼠HDACs mRNA水平的影响。在抑郁症中，HDAC 2和5 mRNA的表达在抑郁状态下增加，而不是在缓解状态下，与对照组相比。在BPD中，HDAC 4 mRNA的表达仅在抑郁状态下增加，而HDAC 6和8的表达在抑郁和缓解状态下与对照组相比均降低，而一级亲属的表达水平未显示出任何显着变化。动物研究表明，HDAC 2和5或HDAC 4，6和8的mRNA在小鼠白细胞中的表达不受抗抑郁药或情绪稳定剂的慢性治疗的影响。我们的数据表明，HDACs的表达改变引起的异常转录调控与心境障碍的病理生理学有关。(C)2009爱思唯尔有限公司保留所有权利。
Chromatin remodeling such as changes in histone acetylation has been suggested to play an important role in the pathophysiology and treatment of mood disorders. In the present study, we investigated whether the expression of histone deacetylase (HDAC) genes are altered in mood disorder patients. We used quantitative real-time PCR to measure the mRNA levels of 11 HDACs (HDAC1-11) in peripheral white blood cells of major depressive disorder (MDD) and bipolar disorder (BPD) patients during depressive and remissive episodes and in the first-degree relatives of BPD patients. In addition, we investigated the effect of antidepressants and mood stabilizers on the mRNA levels of HDACs using mice. In MDD, the expression of HDAC2 and 5 mRNA was increased in a depressive state, but not in a remissive state, compared to controls. In BPD, the expression of HDAC4 mRNA was increased only in a depressive state, and the expression of HDAC6 and 8 was decreased in both depressive and remissive states compared to controls, whereas the first-degree relatives did not show any significant alteration in expression levels. Animal study showed that the expression of HDAC2 and 5 or HDAC4, 6 and 8 mRNAs in the mouse leukocytes were not affected by chronic treatment with antidepressants or mood stabilizers. Our data suggest that aberrant transcriptional regulation caused by the altered expression of HDACs is associated with the pathophysiology of mood disorders. (C) 2009 Elsevier Ltd. All rights reserved.