Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
J Psychiatr Res. 2010 Apr;44(5):263-70. doi: 10.1016/j.jpsychires.2009.08.015. Epub 2009 Sep 19.
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.
染色质重塑，如组蛋白乙酰化的改变，被认为在心境障碍的病理生理学和治疗中发挥重要作用。在本研究中，我们调查了组蛋白去乙酰化酶 (HDAC) 基因的表达是否在心境障碍患者中发生改变。我们使用定量实时 PCR 测量了外周白细胞中 11 种 HDACs（HDAC1-11）在重性抑郁障碍（MDD）和双相障碍（BPD）患者抑郁和缓解期以及 BPD 患者一级亲属中的 mRNA 水平。此外，我们还使用小鼠研究了抗抑郁药和心境稳定剂对 HDACs mRNA 水平的影响。在 MDD 中，与对照组相比，HDAC2 和 -5 mRNA 的表达在抑郁状态下增加，但在缓解状态下没有增加。在 BPD 中，仅在抑郁状态下 HDAC4 mRNA 的表达增加，与对照组相比，在抑郁和缓解状态下 HDAC6 和 -8 的表达降低，而一级亲属的表达水平没有任何显著改变。动物研究表明，慢性抗抑郁药或心境稳定剂治疗不会影响小鼠白细胞中 HDAC2 和 -5 或 HDAC4、-6 和 -8 mRNAs 的表达。我们的数据表明，由 HDACs 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。
