title: In vitro effects of bisphenol A on developing hypothalamic neurons.
abstract: Estradiol plays an essential role in sexual differentiation of the rodent hypothalamus. Endocrine disruptors with estrogenic activity such as bisphenol A (BPA) are reported to disturb sexual differentiation of the hypothalamus. The purpose of the present study was to examine in vitro effects of BPA on developing hypothalamic neurons by focusing on a presynaptic protein synapsin I and microtubule-associated protein 2 (MAP2). In cultured hypothalamic cells from fetal rats, treatment with BPA enhanced both dendritic and synaptic development, as evidenced by increases in the area of dot-like staining of synapsin I and MAP2-positive area. An estrogen receptor (ER) antagonist, ICI 182,780, only partially blocked BPA-induced increase in the synapsin I-area, while it suppressed the MAP2-area increased by BPA. A specific ERK inhibitor, U0126, reduced the synapsin I-area without affecting the MAP2-area. BPA significantly decreased protein levels of synapsin I phosphorylated at Ser-9 and Ser-603. These findings indicate that BPA-inducing effects on dendritic and synaptic development are mediated by different molecular pathways.
authors.affiliation: Department of Life Sciences, Toyo University, 1-1-1 Itakura, Oura, Gunma 374-0193, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwakura
authors.forename: Makiko
authors.initials: M
authors.lastname: Iwafuchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Muraoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Yokosuka
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiga
authors.forename: Chiho
authors.initials: C
authors.lastname: Watanabe
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ohtani-Kaneko
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D000077267:Fulvestrant; D008869:Microtubule-Associated Proteins; D010636:Phenols; D016704:Synapsins; C006780:bisphenol A; D000098826:Bisphenol A Compounds