State-dependent changes in the expression of DNA methyltransferases in mood disorder patients
State-dependent changes in the expression of DNA methyltransferases in mood disorder patients
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DOI：
10.1016/j.jpsychires.2011.04.008
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发表时间：
2011-10-01
影响因子：
4.8
通讯作者：
Watanabe, Yoshifumi
中科院分区：
文献类型：
--
作者：
Higuchi, Fumihiro;Uchida, Shusaku;Watanabe, Yoshifumi
异常转录调控可能是心境障碍病理生理学的重要组成部分。DNA甲基化通常作为一种表观遗传的基因沉默机制，由一组称为DNA甲基转移酶(DNMT)的酶催化。一些证据表明，在神经精神障碍患者和精神障碍动物模型中，DNA甲基化异常。然而，DNMT在心境障碍的病理生理学中的作用还不完全清楚。在这项研究中，我们的目的是确定在情绪障碍患者中是否存在Dnmts基因表达的变化。我们用实时定量聚合酶链式反应检测了重度抑郁障碍(MDD)和双相情感障碍(BPD)患者在抑郁发作和缓解期外周血白细胞中四种DNMT亚型的mRNA表达。我们发现，抑郁状态下DNMT1的表达水平显著降低，但在MDD和BPD的缓解状态下，DNMT1的表达水平并不明显。此外，抑郁状态下MDD患者Dnmt3b基因表达水平显著升高，而缓解期患者Dnmt3b基因表达水平无明显变化。因此，我们的数据表明，DNMT1和DNMT3b的表达变化是状态依赖的，由DNMT1和Dnmt3b的表达变化引起的表观基因调控异常可能与心境障碍的病理生理有关。(C)2011爱思唯尔有限公司。保留所有权利。
Aberrant transcriptional regulation may be one of the key components of the pathophysiology of mood disorders. DNA methylation generally acts as an epigenetic gene silencing mechanism and is catalyzed by a group of enzymes known as DNA methyltransferases (DNMTs). Several lines of evidence have suggested aberrant DNA methylation in patients with neuropsychiatric disorders and in animal models for psychiatric disorders. However, the involvement of DNMTs in the pathophysiology of mood disorders is not completely understood. In this study, we aimed to determine whether there are alterations in the expression of DNMTs mRNA in mood disorder patients. We used quantitative real-time PCR to measure the mRNA expression of four DNMT isoforms in the peripheral white blood cells of major depressive disorder (MDD) and bipolar disorder (BPD) patients during a depressive and a remissive episode. We found that the levels of DNMT1 mRNA were significantly decreased in a depressive but not in a remissive state of MDD and BPD. In addition, the levels of DNMT3B mRNA in MDD were significantly increased in a depressive but not in a remissive state. Thus, our data suggest that the altered expression of DNMTs is state dependent and that the aberrant epigenetic gene regulations caused by the altered expression of DNMT1 and DNMT3B may be associated with the pathophysiology of mood disorders. (C) 2011 Elsevier Ltd. All rights reserved.