Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: effect of maternal deprivation.

ABSTRACT

Early in life, there is a delicate and critical balance aimed to maintain low hormone responses derived from the stress responsive hypothalamic-pituitary-adrenal axis (HPA). However, in the infant rat hypothalamic corticotrophin-releasing hormone (CRH) stress responses to environmental events are clearly seen even though other elements of the HPA axis may have limited responses. In view of the role of CRH in mediating behavior associated with stress and anxiety, we considered the ontogeny and the effects of prolonged maternal deprivation (DEP) in brain areas that express CRH-related molecules outside the hypothalamus. We hypothesized that DEP would alter the ontogeny of CRH, CRH binding protein and CRH receptor 1 in prefrontal cortex, amygdala, septum and hippocampus, areas that are part of the CRH extra hypothalamic system, and that a differential modulation would be observed in response to restraint. We compared non-deprived animals to animals subjected to 24 h of DEP at 6, 12 and 18 days of life. We found (1) developmental patterns, which were idiosyncratic to the anatomical area examined, and (2) a temporal response of mRNA levels which was also site specific. The genomic changes are not always related to maternal deprivation status, in fact DEP enhanced, suppressed or had no consequence on the underlying ontogenic progression and restraint response of these CRH-related molecules. We conclude that the extra hypothalamic CRH system is a dynamic system responding to developmental and environmental demands challenging the basic assumption of stress hypo responsiveness in the infant rat. This modulation may have important repercussions on morphological organization and events leading to neuroprotection.