title: Bisphenol-A rapidly enhanced passive avoidance memory and phosphorylation of NMDA receptor subunits in hippocampus of young rats.
abstract: Bisphenol-A (BPA), an endocrine disruptor, is found to influence development of brain and behaviors in rodents. The previous study indicated that perinatal exposure to BPA impaired learning-memory and inhibited N-methyl-D-aspartate receptor (NMDAR) subunits expressions in hippocampus during the postnatal development in rats; and in cultured hippocampal neurons, BPA rapidly promotes dynamic changes in dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDAR subunit NR2B. In the present study, we examined the rapid effect of BPA on passive avoidance memory and NMDAR in the developing hippocampus of Sprague-Dawley rats at the age of postnatal day 18. The results showed that BPA or estradiol benzoate (EB) rapidly extended the latency to step down from the platform 1 h after footshock and increased the phosphorylation levels of NR1, NR2B, and mitogen-activated extracellular signal-regulated kinase (ERK) in hippocampus within 1 h. While 24 h after BPA or EB treatment, the improved memory and the increased phosphorylation levels of NR1, NR2B, ERK disappeared. Furthermore, pre-treatment with an estrogen receptors (ERs) antagonist, ICI182,780, or an ERK-activating kinase inhibitor, U0126, significantly attenuated EB- or BPA-induced phosphorylations of NR1, NR2B, and ERK within 1 h. These data suggest that BPA rapidly enhanced short-term passive avoidance memory in the developing rats. A non-genomic effect via ERs may mediate the modulation of the phosphorylation of NMDAR subunits NR1 and NR2B through ERK signaling pathway.
authors.affiliation: Chemistry and Life Science College, Zhejiang Normal University, China. xuxh63@zjnu.cn
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Luo
authors.forename: Xing
authors.initials: X
authors.lastname: Hong
authors.forename: Lingdan
authors.initials: L
authors.lastname: Xie
authors.forename: Dong
authors.initials: D
authors.lastname: Tian
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000077267:Fulvestrant; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002070:Butadienes; D052244:Endocrine Disruptors; D004791:Enzyme Inhibitors; D004958:Estradiol; D004965:Estrogen Antagonists; D048049:Extracellular Signal-Regulated MAP Kinases; D000077267:Fulvestrant; D009570:Nitriles; D010636:Phenols; D016194:Receptors, N-Methyl-D-Aspartate; C113580:U 0126; C006780:bisphenol A; D000098826:Bisphenol A Compounds