Rong Zhou1, Fang Chen1, Xuejiao Feng2, Libin Zhou2, Yingchun Li2, Ling Chen3. 1. State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China. 2. Department of Physiology, Nanjing Medical University, Nanjing 210029, China. 3. Department of Physiology, Nanjing Medical University, Nanjing 210029, China. Electronic address: lingchen@njmu.edu.cn.
Abstract
AIMS: The present study focuses on detecting anxiety-like behavior and associated neurochemical alterations in adolescent rats exposed perinatally to bisphenol A (BPA), an estrogen-mimicking endocrine disrupter and investigating the possible involvement of metabotropic glutamate 2/3 receptors (mGlu2/3 receptors) in BPA-induced anxiogenic effects. METHODS AND RESULTS: When female breeders were administered orally with BPA (40 μg/kg/d) during pregnancy and lactation, their pups (here named 'BPA-exposed offspring') developed an anxiety-like phenotype, characterized by the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, impaired glucocorticoid receptor (GR)-mediated negative feedback regulation of the HPA axis, altered hippocampal synaptic plasticity and increased anxiety-like behaviors. BPA-exposed offspring also showed a reduced expression of mGlu2/3 receptors in the hippocampus. BPA-exposed offspring further subjected to systemic administration of mGlu2/3 receptor agonist (LY379268, 0.5 mg/kg, i.p.) or antagonist (LY341495, 1.5 mg/kg, i.p.) twice per day for 6 days. The results indicated that chronic LY379268 treatment corrected the anxiety-like behaviors and associated neurochemical and endocrinological alterations in BPA-exposed offspring. CONCLUSION: Our data demonstrate for the first time that the perinatal BPA exposure induces an anxiety-like phenotype in behaviors and -related neuroendocrinology, and suggest that the changes in mGlu2/3 receptor might lie at the core of the pathological reprogramming triggered by early-life adversity. mGlu2/3 receptor may serve as a novel biomarker and potential therapeutic target for anxiety disorders associated with adverse early-life agents including perinatal BPA exposure.
AIMS: The present study focuses on detecting anxiety-like behavior and associated neurochemical alterations in adolescent rats exposed perinatally to bisphenol A (BPA), an estrogen-mimicking endocrine disrupter and investigating the possible involvement of metabotropic glutamate 2/3 receptors (mGlu2/3 receptors) in BPA-induced anxiogenic effects. METHODS AND RESULTS: When female breeders were administered orally with BPA (40 μg/kg/d) during pregnancy and lactation, their pups (here named 'BPA-exposed offspring') developed an anxiety-like phenotype, characterized by the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, impaired glucocorticoid receptor (GR)-mediated negative feedback regulation of the HPA axis, altered hippocampal synaptic plasticity and increased anxiety-like behaviors. BPA-exposed offspring also showed a reduced expression of mGlu2/3 receptors in the hippocampus. BPA-exposed offspring further subjected to systemic administration of mGlu2/3 receptor agonist (LY379268, 0.5 mg/kg, i.p.) or antagonist (LY341495, 1.5 mg/kg, i.p.) twice per day for 6 days. The results indicated that chronic LY379268 treatment corrected the anxiety-like behaviors and associated neurochemical and endocrinological alterations in BPA-exposed offspring. CONCLUSION: Our data demonstrate for the first time that the perinatal BPA exposure induces an anxiety-like phenotype in behaviors and -related neuroendocrinology, and suggest that the changes in mGlu2/3 receptor might lie at the core of the pathological reprogramming triggered by early-life adversity. mGlu2/3 receptor may serve as a novel biomarker and potential therapeutic target for anxiety disorders associated with adverse early-life agents including perinatal BPA exposure.