Hypothalamic-pituitary-adrenal axis hyperactivity accounts for anxiety-and depression-like behaviors in rats perinatally exposed to bisphenol A

Accumulating studies have proved that perinatal exposure to environmental dose causes long-term potentiation in anxiety/depression-related behaviors in rats.Hyperactivity of the hypothalamic-pituitary-adrenal(HPA) axis is one of the most consistent biological findings in anxiety- and depression-related disorders.The HPA axis is reported to be susceptible to developmental reprogramming.The present study focused on HPA reactivity in postnatal day(PND) 80 male rats exposed perinatally to environmental-dose BPA.When female breeders were orally administered 2 μg/(kg.day) BPA from gestation day 10 to lactation day 7,their offspring(PND 80 BPA-exposed rats)showed obvious anxiety/depression-like behaviors.Notably,significant increase in serum corticosterone and adrenocorticotropin,and corticotropin-releasing hormone mRNA were detected in BPA-exposed rats before or after the mild stressor.Additionally,the level of glucocorticoid receptor mRNA in the hippocampus,but not the hypothalamus,was decreased in BPA-exposed rats.The levels of hippocampal mineralocorticoid receptor mRNA,neuronal nitric oxide synthase and phosphorylated cAMP response element binding protein were increased in BPA-exposed rats.In addition,the testosterone level was in BPA-exposed rats.The results indicate that reprogramming-induced hyperactivity of the HPA axis is an important link between perinatal BPA exposure and persistent potentiation in anxiety and depression.