M10 HPA axis and chronic stress

Title

The hypothalamic-pituitary-adrenal (HPA) axis coordinates the systemic physiological response to stress through a sequential hormonal cascade: stress induces the release of corticotropin-releasing hormone (CRH) in the hypothalamus, which stimulates the secretion of adrenocorticotropic hormone (ACTH) in the pituitary, which in turn stimulates the secretion of cortisol in the adrenal cortex, here extending more completely the cortisol dynamics already introduced in the major depression model (A8). Circulating cortisol exerts negative feedback on the hypothalamus and pituitary, closing the regulatory circuit; However, repeated and sustained activation of the axis under chronic stress generates an accumulated allostatic load that progressively desensitizes this feedback mechanism, perpetuating axis deregulation. This chronic imbalance has documented cross-effects on neuroinflammation (linking with M7) and on hippocampal neurogenesis, where sustained elevated cortisol exerts a direct toxic effect on the neuronal population, in addition to the suppression of BDNF already described in A8.

ID:4282