Chen Xing-Shu, Huang Nanxin, Michael Namaka, Xiao Lan
Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University Chongqing, China.
College of Pharmacy and Medicine, Joint Laboratory of Biological Psychiatry Between Shantou University Medical College and the College of Medicine, University of Manitoba Winnipeg, MB, Canada.
Front Cell Neurosci. 2015 Dec 2;9:451. doi: 10.3389/fncel.2015.00451. eCollection 2015.
Schizophrenia (SZ) is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells.
精神分裂症(SZ)是一种慢性重症精神疾病,目前尚无治愈方法。目前,尚不清楚SZ潜在发病机制中的确切分子机制。该疾病被认为是由遗传、生物、心理和环境因素共同作用引起的。最近的研究表明,表观遗传调控参与了SZ的病理过程。具体而言,DNA甲基化作为最早发现的表观遗传修饰之一,已被广泛认为与神经元功能的调节有关,进而导致诸如SZ等精神疾病。然而,越来越多的证据表明,神经胶质细胞,尤其是功能失调的少突胶质细胞会发生DNA甲基化变化,这有助于SZ的发病机制。本综述主要关注SZ中神经胶质功能障碍所涉及的DNA甲基化。阐明这一机制可能会通过纠正神经胶质细胞中的异常甲基化,开发出治疗SZ和其他疾病的新治疗干预策略。