Glucocorticoids, epigenetic control and stress resilience.
Glucocorticoids, epigenetic control and stress resilience.
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DOI：
10.1016/j.ynstr.2014.10.001
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发表时间：
2015-01
影响因子：
5
通讯作者：
Linthorst AC
中科院分区：
文献类型：
--
作者：
Reul JM;Collins A;Saliba RS;Mifsud KR;Carter SD;Gutierrez-Mecinas M;Qian X;Linthorst AC
糖皮质激素在应对压力挑战中起着关键作用。应激后糖皮质激素分泌的激增需要根据挑战的性质和严重性严格控制其峰值高度、曲率和持续时间等特征。这一点很重要，因为慢性反应过度或反应不足会增加患与压力有关的精神障碍的风险，从而对健康有害。适当的糖皮质激素对应激反应是适应的关键。因此，严格控制基线和应激引起的糖皮质激素分泌是生物体恢复力的重要组成部分。在这里，我们讨论了一些机制，说明了保障糖皮质激素功能控制的措施的多样性和复杂性。这些机制包括矿化皮质激素（MR）和糖皮质激素受体（GR）的占用和浓度的控制，糖皮质激素结合球蛋白（CBG）对游离糖皮质激素可用性的动态控制，以及糖皮质激素在信号、表观遗传和基因组水平上对应激基因转录反应的控制。我们回顾了定期运动对下丘脑轴和睡眠生理以及认知和焦虑相关行为的有益影响。此外，我们描述，可能通过改变gaba能系统，运动减少了压力对信号通路的影响，特别是在齿状回中，这与对压力源的行为反应密切相关。这些观察结果强调了生活方式对压力恢复能力的影响。最后，我们讨论了影响糖皮质激素作用的单核苷酸多态性（snp）如何损害应激恢复能力，这在儿童虐待的情况下最为明显。
Glucocorticoid hormones play a pivotal role in the response to stressful challenges. The surge in glucocorticoid hormone secretion after stress needs to be tightly controlled with characteristics like peak height, curvature and duration depending on the nature and severity of the challenge. This is important as chronic hyper- or hypo-responses are detrimental to health due to increasing the risk for developing a stress-related mental disorder. Proper glucocorticoid responses to stress are critical for adaptation. Therefore, the tight control of baseline and stress-evoked glucocorticoid secretion are important constituents of an organism's resilience. Here, we address a number of mechanisms that illustrate the multitude and complexity of measures safeguarding the control of glucocorticoid function. These mechanisms include the control of mineralocorticoid (MR) and glucocorticoid receptor (GR) occupancy and concentration, the dynamic control of free glucocorticoid hormone availability by corticosteroid-binding globulin (CBG), and the control exerted by glucocorticoids at the signaling, epigenetic and genomic level on gene transcriptional responses to stress. We review the beneficial effects of regular exercise on HPA axis and sleep physiology, and cognitive and anxiety-related behavior. Furthermore, we describe that, possibly through changes in the GABAergic system, exercise reduces the impact of stress on a signaling pathway specifically in the dentate gyrus that is strongly implicated in the behavioral response to that stressor. These observations underline the impact of life style on stress resilience. Finally, we address how single nucleotide polymorphisms (SNPs) affecting glucocorticoid action can compromise stress resilience, which becomes most apparent under conditions of childhood abuse.