Abstract
Maternal stress is a key risk factor in the development of offspring. We previously identified prenatal cold stress-induced anxiety-like behavior reduced in the offspring of rats along with negative feedback regulation from the maternal hippocampus on the hypothalamic-pituitary-adrenal (HPA) axis during prenatal cold stress. However, the precise function of the maternal hypothalamus response to cold stress during late pregnancy in rats has not yet been determined. Therefore, we examined proteins in the hypothalamus that respond to aldosterone, neurodevelopment, inflammation and apoptosis. Our results show that prenatal cold stress induced the expression of mineralocorticoid receptors (MR) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), suggesting prenatal cold stress may promote the elevation of aldosterone levels in the hypothalamus. Remarkably, increased expression of brain derived neurotrophic factor (BDNF) helped to replenish intracellular peptidergic stores and ensure homeostatic balance during prenatal cold stress. Furthermore, prenatal cold stress reduced the expression of c-Fos via STAT3 and ERK1/2 pathways in the hypothalamus. Moreover, prenatal cold stress induced NF-κB phosphorylation at Ser536, then promoted the expression of inducible nitric oxide synthase (iNOS) and induced an apoptosis-related protein response. Together, this study confirms that changes in the maternal hypothalamus during cold stress in late pregnancy are directly reflective of the response of the HPA to cold stress and demonstrates how the hypothalamus coordinates cold stress. We suggest mechanisms which might explain how these states might be linked with an abnormal stress response.