Cheng Ziqian, Su Jingyun, Zhang Kai, Jiang Huiyi, Li Bingjin
Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, Second Hospital of Jilin University, Changchun, China.
Engineering Lab on Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, China.
Front Cell Dev Biol. 2022 Jul 5;10:929732. doi: 10.3389/fcell.2022.929732. eCollection 2022.
Depression has an alarmingly high prevalence worldwide. A growing body of evidence indicates that environmental factors significantly affect the neural development and function of the central nervous system and then induce psychiatric disorders. Early life stress (ELS) affects brain development and has been identified as a major cause of depression. It could promote susceptibility to stress in adulthood. Recent studies have found that ELS induces epigenetic changes that subsequently affect transcriptional rates of differentially expressed genes. The epigenetic modifications involved in ELS include histone modifications, DNA methylation, and non-coding RNA. Understanding of these genetic modifications may identify mechanisms that may lead to new interventions for the treatment of depression. Many reports indicate that different types of ELS induce epigenetic modifications of genes involved in the neurotransmitter systems, such as the dopaminergic system, the serotonergic system, the gamma-aminobutyric acid (GABA)-ergic system, and the glutamatergic system, which further regulate gene expression and ultimately induce depression-like behaviors. In this article, we review the effects of epigenetic modifications on the neurotransmitter systems in depression-like outcomes produced by different types of ELS in recent years, aiming to provide new therapeutic targets for patients who suffer from depression.
抑郁症在全球的患病率高得惊人。越来越多的证据表明，环境因素会显著影响中枢神经系统的神经发育和功能，进而诱发精神疾病。早年生活应激（ELS）会影响大脑发育，并且已被确认为抑郁症的主要成因。它会增加成年后患应激相关疾病的易感性。最近的研究发现，ELS会诱导表观遗传变化，进而影响差异表达基因的转录速率。与ELS相关的表观遗传修饰包括组蛋白修饰、DNA甲基化和非编码RNA。了解这些基因修饰可能会找出一些机制，从而带来治疗抑郁症的新干预措施。许多报告表明，不同类型的ELS会诱导参与神经递质系统的基因发生表观遗传修饰，如多巴胺能系统、5-羟色胺能系统、γ-氨基丁酸（GABA）能系统和谷氨酸能系统，这些系统会进一步调节基因表达并最终诱发类似抑郁的行为。在本文中，我们综述了近年来表观遗传修饰对不同类型ELS所产生的类似抑郁结果中的神经递质系统的影响，旨在为抑郁症患者提供新的治疗靶点。
