title: Hypothalamic-pituitary-adrenal axis hyperactivity accounts for anxiety- and depression-like behaviors in rats perinatally exposed to bisphenol A.
abstract: 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.
authors.affiliation: State Key Lab of Reproductive Medicine.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Lab of Reproductive Medicine.
authors.forename: Yinyang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
keywords: BPA; HPA axis; affective behaviors; glucocorticoid receptor; testosterone