title: Nanomolar dose of bisphenol A rapidly modulates spinogenesis in adult hippocampal neurons.
abstract: We demonstrated the rapid effects of 10nM bisphenol A (BPA) on the spinogenesis of adult rat hippocampal slices. The density of spines was analyzed by imaging Lucifer Yellow-injected CA1 neurons in slices. Not only the total spine density but also the head diameter distribution of spine was quantitatively analyzed. Spinogenesis was significantly enhanced by BPA within 2h. In particular, the density of middle-head spine (with head diameter of 0.4-0.5μm) was significantly increased. Hydroxytamoxifen, an antagonist of both estrogen-related receptor gamma (ERRγ) and estrogen receptors (ERα/ERβ), blocked the BPA-induced enhancement of the spine density. However, ICI 182,780, an antagonist of ERα/ERβ, did not suppress the BPA effects. Therefore, ERRγ is deduced to be a high affinity receptor of BPA, responsible for modulation of spinogenesis. The BPA-induced enhancement of spinogenesis was also suppressed by MAP kinase inhibitor, PD98059, and the blocker of NMDA receptors, MK-801. Washout of BPA for additional 2h after 2h BPA treatment abolished the BPA-induced enhancement of spinogenesis, suggesting that the BPA effect was reversible. ERRγ was localized at synapses as well as cell bodies of principal neurons. ERRγ at synapses may contribute to the observed rapid effect. The level of BPA in the hippocampal slices was determined by mass-spectrometric analysis.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanabe
authors.forename: Hinako
authors.initials: H
authors.lastname: Yoshino
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.forename: Mari
authors.initials: M
authors.lastname: Ogiue-Ikeda
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shimohigashi
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000494:pharmacology; D000077267:Fulvestrant; D006624:Hippocampus / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D016291:Dizocilpine Maleate; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005419:Flavonoids; D000077267:Fulvestrant; D020928:Mitogen-Activated Protein Kinases; D010636:Phenols; D011960:Receptors, Estrogen; D016194:Receptors, N-Methyl-D-Aspartate; D013629:Tamoxifen; C493778:Esrrg protein, rat; C016601:afimoxifene; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one