title: Perinatal exposure to low-dose of bisphenol A causes anxiety-like alteration in adrenal axis regulation and behaviors of rat offspring: a potential role for metabotropic glutamate 2/3 receptors.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors: Rong
authors: R
authors: Zhou
authors: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors: Fang
authors: F
authors: Chen
authors: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors: Xuejiao
authors: X
authors: Feng
authors: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors: Libin
authors: L
authors: Zhou
authors: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors: Yingchun
authors: Y
authors: Li
authors: Department of Physiology, Nanjing Medical University, Nanjing 210029, China. Electronic address: lingchen@njmu.edu.cn.
authors: Ling
authors: L
authors: Chen
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001007:Anxiety / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D001559:Benzhydryl Compounds / Q000633:toxicity*; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D000324:Adrenocorticotropic Hormone; D000893:Anti-Inflammatory Agents; D001559:Benzhydryl Compounds; D003345:Corticosterone; D003907:Dexamethasone; D004968:Estrogens, Non-Steroidal; D018683:Excitatory Amino Acid Agents; D010636:Phenols; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Anxiety; BPA; GR; HPA-axis; mGlu2/3 receptor