Abstract
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 these issues, a chronic stress paradigm for the neonatal rat, using limited bedding material to alter the cage environment, was devised. In 9-day-old rats subjected to this chronic stress for 1 week, significant and striking changes in the expression and release patterns of key molecules that govern the neuroendocrine stress responses were observed. The presence of sustained stress was evident from enhanced activation of peripheral elements of the neuroendocrine stress response, i.e. increased basal plasma corticosterone concentrations, high adrenal weight and decreased body weight. Central regulatory elements of the neuroendocrine stress response were perturbed, including reduced expression of hypothalamic corticotropin-releasing hormone that, surprisingly, was accompanied by reduced glucocorticoid receptor expression. Thus, the effects of chronic sustained stress in the neonatal rat on the hypothalamic-pituitary-adrenal axis included substantial changes in the expression and activity of major regulators of this axis. Importantly, the changes induced by this chronic stress differed substantially from those related to acute or recurrent stress, providing a novel model for studying the long-term effects of chronic, early life stress on neuroendocrine functions throughout life.
Highlights
In both humans and experimental animals, stress early in life may lead to affective and anxiety disorders [1, 2]
The current study demonstrates that altering cage environment via limitation of bedding material leads to significant chronic stress in the immature rat, associated with changes in gene expression at multiple levels of the HPA axis
corticotropin releasing hormone (CRH) mRNA expression in paraventricular nucleus (PVN) was reduced, yet decreased pituitary CRH binding capacity was consistent with enhanced hypothalamic CRH release during this chronic stress
Summary
In both humans and experimental animals, stress early in life may lead to affective and anxiety disorders [1, 2]. A longer (24 h) maternal deprivation stress did not influence CRH gene expression [7]; but see Smith et al [8], who reported reduced CRH mRNA expression These data indicate that the influence of a single or recurrent acute stress, as well as that of more protracted stressful experiences, on molecules involved in the neuroendocrine stress response may be highly variable and not predictive of the effects of chronic stress. The goals of the present study were to gain insight into the short-term effects of chronic psychological stress on the molecules that comprise the HPA axis in immature rats This information should provide a key to understanding the mechanisms by which chronic early life stress influences the response to subsequent stressors later in life. Parameters indicating the presence of chronic stress, i.e. body and adrenal weights and basal plasma corticosterone (CORT), were examined
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