Mifsud Karen R, Reul Johannes M H M
a Neuro-Epigenetics Research Group, Bristol Medical School , University of Bristol , Bristol , UK.
Stress. 2018 Sep;21(5):389-402. doi: 10.1080/10253890.2018.1456526. Epub 2018 Apr 4.
Successful coping with stressful events involves adaptive and cognitive processes in the brain that make the individual more resilient to similar stressors in the future. Stressful events result in the secretion of glucocorticoids (GCs) from the adrenal glands into the blood stream. Early work proved instrumental for developing the concept that these hormones act in the brain to coordinate physiological and behavioral responses to stress through binding to two different GC-binding receptors. Once activated these receptors translocate to the nucleus where they act on target genes to facilitate (or sometimes inhibit) transcription. There are two types of receptors in the brain, the mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). This review summarizes recent work which provides new insights regarding the genomic action of these receptors, both under baseline conditions and following exposure to acute stress. This work is discussed alongside the extensive studies undertaken in this field previously and new, and exciting "big data" studies which have generated a wealth of relevant data. The consequence of these new insights will challenge existing assumptions about the role of MRs and GRs and pave the way for the implementation of novel and improved methodologies to identify the role these corticosteroid receptors have in stress-related behavioral adaptation.
成功应对压力事件涉及大脑中的适应性和认知过程，这些过程使个体在未来面对类似压力源时更具恢复力。压力事件会导致肾上腺分泌糖皮质激素（GCs）进入血流。早期的研究对于形成这样的概念起到了重要作用，即这些激素在大脑中通过与两种不同的糖皮质激素结合受体结合来协调对压力的生理和行为反应。一旦被激活，这些受体就会转移到细胞核，在那里它们作用于靶基因以促进（有时是抑制）转录。大脑中有两种受体，盐皮质激素受体（MR）和糖皮质激素受体（GR）。本综述总结了近期的研究工作，这些工作为这些受体在基线条件下以及暴露于急性应激后的基因组作用提供了新的见解。这项工作将与该领域先前进行的广泛研究以及新的、令人兴奋的“大数据”研究一起进行讨论，这些“大数据”研究已经产生了大量相关数据。这些新见解的结果将挑战关于MRs和GRs作用的现有假设，并为实施新颖且改进的方法以确定这些皮质类固醇受体在与压力相关的行为适应中的作用铺平道路。
