Trollope Alexandra F, Mifsud Karen R, Saunderson Emily A, Reul Johannes M H M
Neuro-Epigenetics Research Group, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
Department of Anatomy, College of Medicine and Dentistry, James Cook University, Townsville 4811, Australia.
Epigenomes. 2017 Dec;1(3):17. doi: 10.3390/epigenomes1030017. Epub 2017 Nov 2.
Consolidation of contextual memories after a stressful encounter is essential for the survival of an organism and in allowing a more appropriate response to be elicited should the perceived threat reoccur. Recent evidence has explored the complex role that epigenetic mechanisms play in the formation of such memories, and the underlying signaling pathways are becoming more apparent. The glucocorticoid receptor (GR) has been shown to play a key role in these events having both genomic and non-genomic actions in the brain. GR has been shown to interact with the extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) signaling pathway which, in concert, drives epigenetic modifications and chromatin remodeling, resulting in gene induction and memory consolidation. Evidence indicates that stressful events can have an effect on the offspring in utero, and that epigenetic marks altered early in life may persist into adulthood. A new and controversial area of research, however, suggests that epigenetic modifications could be inherited through the germline, a concept known as transgenerational epigenetics. This review explores the role that epigenetic processes play in the central nervous system, specifically in the consolidation of stress-induced memories, the concept of transgenerational epigenetic inheritance, and the potential role of epigenetics in revolutionizing the treatment of stress-related disorders through the emerging field of pharmacoepigenetics and personalized medical treatment.
应激遭遇后情境记忆的巩固对于生物体的生存至关重要，并且在感知到的威胁再次出现时能够引发更恰当的反应。最近的证据探讨了表观遗传机制在这类记忆形成中所起的复杂作用，其潜在的信号通路也越来越清晰。糖皮质激素受体（GR）已被证明在这些事件中起关键作用，在大脑中具有基因组和非基因组作用。GR已被证明与细胞外信号调节激酶丝裂原活化蛋白激酶（ERK MAPK）信号通路相互作用，协同驱动表观遗传修饰和染色质重塑，从而导致基因诱导和记忆巩固。有证据表明，应激事件可能会对子宫内的后代产生影响，并且生命早期改变的表观遗传标记可能会持续到成年期。然而，一个新的且有争议的研究领域表明，表观遗传修饰可能通过种系遗传，这一概念被称为跨代表观遗传学。本综述探讨了表观遗传过程在中枢神经系统中的作用，特别是在应激诱导记忆的巩固方面，跨代表观遗传遗传的概念，以及表观遗传学在通过新兴的药物表观遗传学和个性化医疗领域彻底改变应激相关疾病治疗方面的潜在作用。
