کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5900613 | 1568827 | 2015 | 21 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: ReviewGABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response ReviewGABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response](/preview/png/5900613.png)
- GABAA receptors (GABAARs) curtail stress-induced activation of the HPA axis.
- Stressful challenges evoke de novo brain synthesis of GABAAR-active neurosteroids (NS).
- NS inhibit the output of CRF-releasing neurones of the hypothalamus.
- NS actions in the hypothalamus are blunted in rodent models of early-life adversity.
- NS may be important molecular messengers in the programming of the stress-response.
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 GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs 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 GABAAR-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.
Journal: Frontiers in Neuroendocrinology - Volume 36, January 2015, Pages 28-48