Behavioral Studies and Genetic Alterations in Corticotropin-Releasing Hormone (CRH) Neurocircuitry: Insights into Human Psychiatric Disorders.
Behavioral Studies and Genetic Alterations in Corticotropin-Releasing Hormone (CRH) Neurocircuitry: Insights into Human Psychiatric Disorders.
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DOI：
10.3390/bs2020135
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发表时间：
2012-06-21
期刊：
影响因子：
--
通讯作者：
Muglia LJ
中科院分区：
文献类型：
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作者：
Laryea G;Arnett MG;Muglia LJ
为了维持健康，所有生物体都需要在不利的生理或心理经历存在下重建稳态的能力。应激时下丘脑-垂体-肾上腺（HPA）轴的调节在防止可能增加情感障碍易感性的适应不良反应方面很重要。促肾上腺皮质激素释放激素（CRH）是HPA轴通路中的一种中枢应激激素，与应激诱导的精神障碍、生殖和心脏功能以及能量代谢有关。在精神疾病的背景下，CRH功能障碍与创伤后应激障碍、重度抑郁症、神经性厌食症和焦虑症的发生相关。本文就CRH的合成、分子信号转导和调控以及突触活性等方面的研究进展作一综述。我们继续总结突变动物模型中CRH信号改变的研究。这些数据表明CRH在神经内分泌、自主神经和行为适应和适应不良中起着重要作用。接下来，我们介绍了与压力和精神疾病相关的CRH通路基因的人类遗传多态性。最后，我们讨论了CRH活性调节剂的作用，作为潜在的治疗干预，旨在治疗与压力相关的适应不良行为的网站。
To maintain well-being, all organisms require the ability to re-establish homeostasis in the presence of adverse physiological or psychological experiences. The regulation of the hypothalamic-pituitary adrenal (HPA) axis during stress is important in preventing maladaptive responses that may increase susceptibility to affective disorders. Corticotropin-releasing hormone (CRH) is a central stress hormone in the HPA axis pathway and has been implicated in stress-induced psychiatric disorders, reproductive and cardiac function, as well as energy metabolism. In the context of psychiatric disorders, CRH dysfunction is associated with the occurrence of post-traumatic stress disorder, major depression, anorexia nervosa, and anxiety disorders. Here, we review the synthesis, molecular signaling and regulation, as well as synaptic activity of CRH. We go on to summarize studies of altered CRH signaling in mutant animal models. This assembled data demonstrate an important role for CRH in neuroendocrine, autonomic, and behavioral correlates of adaptation and maladaptation. Next, we present findings regarding human genetic polymorphisms in CRH pathway genes that are associated with stress and psychiatric disorders. Finally, we discuss a role for regulators of CRH activity as potential sites for therapeutic intervention aimed at treating maladaptive behaviors associated with stress.