In vitro effects of bisphenol A on developing hypothalamic neurons.

Authors :: Iwakura T
Iwafuchi M
Muraoka D
Yokosuka M
Shiga T
Watanabe C
Ohtani-Kaneko R
Source :: Toxicology [Toxicology] 2010 Jun 04; Vol. 272 (1-3), pp. 52-8. Date of Electronic Publication: 2010 Apr 23.
Publication Year :: 2010
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.<br /> (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)