title: Prenatal and postnatal exposure to bisphenol a induces anxiolytic behaviors and cognitive deficits in mice.
abstract: Bisphenol A (BPA), an environmental endocrine-disrupting chemical, has been extensively evaluated for reproductive toxicity and carcinogenicity. However, little is known about the behavioral and neurochemical effects of BPA exposure. This study examined whether chronic daily exposure to an environmental endocrine-disrupting chemical, bisphenol A [(BPA); 100 microg/kg/day or 500 microg/kg/day, p.o.], from prenatal Day 7 to postnatal Day 36 would lead to changes in anxiety and memory in mice. First, we observed the behavioral alterations of BPA-treated mice using two anxiety-related models, the open field test and elevated plus maze (EPM) test. In the open field test, BPA treatment (100 microg/kg/day) increased movement in the central zone. BPA treatment (500 microg/kg/day) also increased the time spent in the open arms in the EPM test. Second, we measured cognitive ability in the Y-maze test and novel object test. BPA-treated mice showed decreased alternation behavior in the Y-maze at both of doses, indicating working memory impairment. BPA-treated mice (100 microg/kg/day) also showed decreased novel object recognition as expressed by central locomotion and frequency in the central zone, showing recognition memory impairment. Finally, to measure changes in the dopaminergic and NMDAergic systems in the brain, we performed autoradiographic receptor binding assays for dopamine D(1) and D(2) receptors, the NMDA receptor, and the dopamine transporter. BPA treatment increased D(2) receptor binding in the caudate putamen (CPu) but decreased DAT binding. BPA treatment also decreased NMDA receptor binding in the frontal cortex and CA1, CA3, and DG of the hippocampus. Taken together, our results suggest that long-term BPA exposure in mice can induce anxiolytic behaviors, cognitive deficits and changes in the dopaminergic and NMDAergic systems.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tian
authors.forename: Joung-Hee
authors.initials: JH
authors.lastname: Baek
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D014151:Anti-Anxiety Agents / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D001523:Mental Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D014151:Anti-Anxiety Agents; D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; C006780:bisphenol A; D000098826:Bisphenol A Compounds