Dong Erbo, Pandey Subhash C
Center for Alcohol Research in Epigenetics, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Center for Alcohol Research in Epigenetics, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States; Jesse Brown VA Medical Center, Chicago, IL, United States.
Int Rev Neurobiol. 2021;156:185-215. doi: 10.1016/bs.irn.2020.08.004. Epub 2020 Sep 26.
New insights into the pathophysiology of psychiatric disorders suggest the existence of a complex interplay between genetics and environment. This notion is supported by evidence suggesting that exposure to stress during pregnancy exerts profound effects on the neurodevelopment and behavior of the offspring and predisposes them to psychiatric disorders later in life. Accumulated evidence suggests that vulnerability to psychiatric disorders may result from permanent negative effects of long-term changes in synaptic plasticity due to altered epigenetic mechanisms (histone modifications and DNA methylation) that lead to condensed chromatin architecture, thereby decreasing the expression of candidate genes during early brain development. In this chapter, we have summarized the literature of clinical studies on psychiatric disorders induced by maternal stress during pregnancy. We also discussed the epigenetic alterations of gene regulations induced by prenatal stress. Because the clinical manifestations of psychiatric disorders are complex, it is obvious that the biological progression of these diseases cannot be studied only in postmortem brains of patients and the use of animal models is required. Therefore, in this chapter, we have introduced a well-established mouse model of prenatal stress (PRS) generated in restrained pregnant dams. The behavioral phenotypes of the offspring (PRS mice) born to the stressed dam and underlying epigenetic changes in key molecules related to synaptic activity were described and highlighted. PRS mice may serve as a useful model for investigating the pathogenesis of psychiatric disorders and may be a useful tool for screening for the potential compounds that may normalize aberrant epigenetic mechanisms induced by prenatal stress.
对精神疾病病理生理学的新见解表明，基因与环境之间存在复杂的相互作用。这一观点得到了相关证据的支持，这些证据表明，孕期暴露于压力之下会对后代的神经发育和行为产生深远影响，并使他们在日后更容易患上精神疾病。越来越多的证据表明，精神疾病的易感性可能源于表观遗传机制（组蛋白修饰和DNA甲基化）改变导致的突触可塑性长期变化所产生的永久性负面影响，这种改变会导致染色质结构浓缩，从而在大脑早期发育过程中降低候选基因的表达。在本章中，我们总结了关于孕期母亲压力所致精神疾病的临床研究文献。我们还讨论了产前压力诱导的基因调控表观遗传改变。由于精神疾病的临床表现复杂，显然这些疾病的生物学进展不能仅在患者的尸检大脑中进行研究，还需要使用动物模型。因此，在本章中，我们介绍了一种在受限制的怀孕母鼠中建立的成熟的产前应激（PRS）小鼠模型。描述并强调了应激母鼠所产后代（PRS小鼠）的行为表型以及与突触活动相关的关键分子的潜在表观遗传变化。PRS小鼠可能是研究精神疾病发病机制的有用模型，也可能是筛选可使产前应激诱导的异常表观遗传机制正常化的潜在化合物的有用工具。
