In vitro effects of bisphenol A on developing hypothalamic neurons

• Published in: Toxicology (Amsterdam) Vol. 272; no. 1; pp. 52 - 58
• Main Authors: Iwakura, Takashi, Iwafuchi, Makiko, Muraoka, Daisuke, Yokosuka, Makoto, Shiga, Takashi, Watanabe, Chiho, Ohtani-Kaneko, Ritsuko
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 04.06.2010; Elsevier
• Subjects: Animals; Benzhydryl Compounds; Biological and medical sciences; BPA; Cells, Cultured; Dendrites - drug effects; Dendrites - metabolism; Development; Emergency; Endocrine Disruptors - pharmacology; ERK; Estradiol - analogs & derivatives; Estradiol - pharmacology; Female; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; MAP2; Medical sciences; Microtubule-Associated Proteins - metabolism; Neurons - drug effects; Neurons - metabolism; Phenols - pharmacology; Rats; Rats, Sprague-Dawley; Synapse; Synapsin I; Synapsins - metabolism; Toxicology; Synapsin I; BPA; Synapse; MAP2; Development; Hypothalamus; ERK; Extracellular signal-regulated protein kinase; Enzyme; Transferases; Central nervous system; Mitogen-activated protein kinase; Endocrine disruptor; In vitro; Encephalon; Bisphenol A; Neuron
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2010.04.005

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.