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Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: effect of maternal deprivation
Delia M Vazquez1, Charles Bailey, Gersham W Dent
1Department of Pediatrics, Endocrine Division, University of Michigan, Ann Arbor, MI 48109-0718, USA. dmvazq@umich.edu
Insights
Early life stress, like maternal deprivation, significantly impacts the developing brain. This study reveals the extra hypothalamic corticotropin-releasing hormone (CRH) system dynamically responds to early life stress and environmental challenges.
Area of Science:
- Neuroscience
- Developmental Biology
- Stress Research
Background:
- The infant rat hypothalamic-pituitary-adrenal (HPA) axis exhibits a delicate balance to maintain low hormone responses.
- Early life stress can disrupt this balance, particularly involving corticotropin-releasing hormone (CRH).
- CRH plays a crucial role in mediating stress and anxiety behaviors.
Purpose of the Study:
- To investigate the effects of prolonged maternal deprivation (DEP) on the ontogeny of CRH-related molecules outside the hypothalamus.
- To examine how DEP and restraint stress alter CRH, CRH binding protein, and CRH receptor 1 in specific brain regions.
- To challenge the notion of stress hypo-responsiveness in infant rats.
Main Methods:
- Comparison of non-deprived and maternally deprived (24h DEP) infant rats at 6, 12, and 18 days of life.
- Analysis of CRH, CRH binding protein, and CRH receptor 1 mRNA levels in the prefrontal cortex, amygdala, septum, and hippocampus.
- Assessment of responses to acute restraint stress.
Main Results:
- Developmental patterns of CRH-related molecules were unique to each brain area.
- The temporal response of mRNA levels to DEP and restraint was site-specific.
- DEP's effects varied, enhancing, suppressing, or having no impact on ontogeny and restraint responses.
Conclusions:
- The extra hypothalamic CRH system is a dynamic network that responds to developmental and environmental challenges.
- Early life stress modulates this system, questioning the assumption of infant rat stress hypo-responsiveness.
- These modulations may influence neural organization and neuroprotection.
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.
