Neurobiology of the stress response early in life: evolution of a concept and the role of corticotropin releasing hormone

Abstract

Over the last few decades, concepts regarding the presence of hormonal and molecular responses to stress during the first postnatal weeks in the rat and the role of the neuropeptide corticotropin releasing hormone (CRH) in these processes, have been evolving. CRH has been shown to contribute critically to molecular and neuroendocrine responses to stress during development. In turn the expression of this neuropeptide in both hypothalamus and amygdala is differentially modulated by single and recurrent stress, and is determined also by the type of stress (eg, psychological or physiological). A likely transcriptional regulatory factor for modulating CRH gene expression, the cAMP responsive element binding protein CREB, is phosphorylated (activated) in the developing hypothalamus within seconds of stress onset, preceding the transcription of the CRH gene and initiating the activation of stress-induced cellular and neuroendocrine cascades. Finally, early life stress may permanently modify the hypothalamic pituitary adrenal axis and the response to further stressful stimuli, and recent data suggest that CRH may play an integral role in the mechanisms of these long-term changes. Molecular Psychiatry (2001) 6, 647-656.

Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent

“…This, supported by the fact that many of the activated neurons in the hippocampal formation expressed the CRF 1 receptor, points to a substantial role of CRH receptor activation in the transduction of stress signals within the hippocampus. Indeed, a role for CRH in stress-evoked neuronal changes has been suggested, 40,43,56,83 in addition to the well established and robust effects of glucocorticoids. 1,28 It should be noted that in the current study, we chose to use Fos and pCREB as markers of neuronal activation.…”

“…41,42 In both mature and immature organisms of several mammalian species, the role of hypothalamic CRH in stress-evoked elevation of plasma glucocorticoids, via activation of CRH receptors within the pituitary gland, has been well established. 2,25,41,43 Contribution of CRH to the effects of stress on neuronal function within the brain has also been delineated, and demonstrates age-dependent properties. For example, central administration of CRH activates neurons in the amygdala, contributing to anxiety-like behaviors 44,45 as well as to memory consolidation.…”

Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling

“…These diverse morphological effects of stress are not surprising, given the wide array of stress types and contexts (24) coupled with the biological variability of the hippocampus that is being stressed, including gender (53,69,70) and age (41,71). Therefore it is reasonable to propose that the plethora of structural and functional changes provoked by stress might be a result of a broad repertoire of stress-activated mediators acting via numerous mechanisms.…”

ABCB1 (MDR1)-Type P-Glycoproteins at the Blood–Brain Barrier Modulate the Activity of the Hypothalamic–Pituitary–Adrenocortical System: Implications for Affective Disorder

“…With respect to the present data, those naturally occurring and functionally relevant polymorphisms of ABCB1 are also likely to affect and modulate the penetration of endogenous glucocorticoid hormones into the central nervous system. Genetic variability of the ABCB1 gene, therefore, may alter an innate setpoint for susceptibility to stress-associated psychiatric disorders (Meaney et al, 1996;Brunson et al, 2001). Whether this might result in persistent changes in the responsiveness and regulation of the HPA system will be the subject of future investigations, correlating both genetic information with individual characteristics of the neuroendocrine phenotype.…”