Gunn Benjamin G, Brown Adam R, Lambert Jeremy J, Belelli Delia
Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, Ninewells Hospital, University of Dundee Dundee, UK.
Front Neurosci. 2011 Dec 5;5:131. doi: 10.3389/fnins.2011.00131. eCollection 2011.
Since the pioneering discovery of the rapid CNS depressant actions of steroids by the "father of stress," Hans Seyle 70 years ago, brain-derived "neurosteroids" have emerged as powerful endogenous modulators of neuronal excitability. The majority of the intervening research has focused on a class of naturally occurring steroids that are metabolites of progesterone and deoxycorticosterone, which act in a non-genomic manner to selectively augment signals mediated by the main inhibitory receptor in the CNS, the GABA(A) receptor. Abnormal levels of such neurosteroids associate with a variety of neurological and psychiatric disorders, suggesting that they serve important physiological and pathophysiological roles. A compelling case can be made to implicate neurosteroids in stress-related disturbances. Here we will critically appraise how brain-derived neurosteroids may impact on the stress response to acute and chronic challenges, both pre- and postnatally through to adulthood. The pathological implications of such actions in the development of psychiatric disturbances will be discussed, with an emphasis on the therapeutic potential of neurosteroids for the treatment of stress-associated disorders.
70年前，“应激之父”汉斯·塞尔耶率先发现了类固醇具有快速的中枢神经系统抑制作用，自那时起，脑源性“神经甾体”已成为神经元兴奋性的强大内源性调节剂。大多数后续研究都集中在一类天然存在的类固醇上，它们是孕酮和脱氧皮质酮的代谢产物，以非基因组方式发挥作用，选择性增强中枢神经系统主要抑制性受体——γ-氨基丁酸A（GABA(A)）受体介导的信号。此类神经甾体水平异常与多种神经和精神疾病相关，表明它们发挥着重要的生理和病理生理作用。有令人信服的理由认为神经甾体与应激相关障碍有关。在此，我们将批判性地评估脑源性神经甾体如何在从产前到成年的整个过程中，对急性和慢性应激挑战的应激反应产生影响。我们将讨论此类作用在精神障碍发展中的病理意义，重点是神经甾体治疗应激相关疾病的潜在治疗价值。
