Altered regulation of gene and protein expression of hypothalamic-pituitary-adrenal axis components in an immature rat model of chronic stress

Chronic stress early in postnatal life influences hormonal and behavioural responses to stress persistently, but the mechanisms and molecular cascades that are involved in this process have not been clarified. To approach the se issues, a chronic stress paradigm for the neonatal rat, using limited be dding material to alter the cage environment, was devised. In 9-day-old rat s subjected to this chronic stress for 1 week, significant and striking cha nges in the expression and release patterns of key molecules that govern th e neuroendocrine stress responses were observed. The presence of sustained stress was evident from enhanced activation of peripheral elements of the n euroendocrine stress response, i.e. increased basal plasma corticosterone c oncentrations, high adrenal weight and decreased body weight. Central regul atory elements of the neuroendocrine stress response were perturbed, includ ing reduced expression of hypothalamic corticotropin-releasing hormone that , surprisingly, was accompanied by reduced glucocorticoid receptor expressi on. Thus, the effects of chronic sustained stress in the neonatal rat on th e hypothalamic-pituitary-adrenal axis included substantial changes in the e xpression and activity of major regulators of this axis. Importantly, the c hanges induced by this chronic stress differed substantially from those rel ated to acute or recurrent stress, providing a novel model for studying the long-term effects of chronic, early life stress on neuroendocrine function s throughout life.