Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Minami-kogushi, Ube, Yamaguchi, Japan.
J Psychiatr Res. 2011 Oct;45(10):1295-300. doi: 10.1016/j.jpsychires.2011.04.008. Epub 2011 May 17.
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.
异常的转录调控可能是心境障碍病理生理学的关键组成部分之一。DNA 甲基化通常作为一种表观遗传基因沉默机制，由一组称为 DNA 甲基转移酶（DNMTs）的酶催化。有几条证据表明神经精神障碍患者和精神障碍动物模型存在异常的 DNA 甲基化。然而，DNMTs 在心境障碍的病理生理学中的参与尚不完全清楚。在这项研究中，我们旨在确定心境障碍患者的 DNMTs mRNA 表达是否存在改变。我们使用定量实时 PCR 测量了在抑郁和缓解期的主要抑郁障碍（MDD）和双相障碍（BPD）患者外周白细胞中四种 DNMT 同工型的 mRNA 表达。我们发现，DNMT1 mRNA 的水平在 MDD 和 BPD 的抑郁状态而非缓解状态下显著降低。此外，MDD 中 DNMT3B mRNA 的水平在抑郁状态而非缓解状态下显著增加。因此，我们的数据表明，DNMTs 的表达改变是状态依赖性的，DNMT1 和 DNMT3B 表达改变引起的异常表观遗传基因调控可能与心境障碍的病理生理学有关。
