期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms22115495
关键词
stress; hypothalamus-pituitary-adrenal axis; neurosteroids; depression; brexanolone; PTSD
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [001]
- CAPES
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [19/2551-0000665-9]
This article discusses the role of the HPA axis under stressful conditions and the importance of allopregnanolone in promoting negative feedback mechanisms to restore homeostasis. Chronic, repeated exposure to stress may lead to dysfunction, contributing to the pathogenesis of major depressive disorder and post-traumatic stress disorder (PTSD).
Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3 alpha,5 alpha-tetrahydroprogesterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.
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