期刊
FRONTIERS IN NEUROENDOCRINOLOGY
卷 36, 期 -, 页码 28-48出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yfrne.2014.06.001
关键词
Allopregnanolone; GABA(A) receptor; HPA axis; Early-life stress; Depression
资金
- Wellbeing of Women-UK [RG1265]
- BBSRC-UK, case award studentship [11426]
- Medical Research Council-UK, studentship (DTG) [MR/K 500896/1]
- Tenovus Scotland
- Medical Research Council [1313951] Funding Source: researchfish
Regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABA(A) receptors (GABA(A)Rs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABA(A)Rs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioural changes associated with early-life adversity. We will appraise how GABA(A)R-active neurosteroids may impact on HPA axis development and the orchestration of the stress-evoked response. The significance of these actions will be discussed in the context of stress-associated mood disorders. (C) 2014 The Authors. Published by Elsevier Inc.
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