Rapid Ca(2+) signaling induced by Bisphenol A in cultured rat hippocampal neurons.
Rapid Ca(2+) signaling induced by Bisphenol A in cultured rat hippocampal neurons.
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发表时间：
2006-02
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通讯作者：
Nobuaki Tanabe;T. Kimoto;S. Kawato
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作者：
Nobuaki Tanabe;T. Kimoto;S. Kawato
双酚A（BPA）是一种典型的内分泌干扰物。我们研究了低剂量BPA诱导培养海马神经元快速Ca（2+）信号转导的机制。材料与方法取3 ~ 5日龄大鼠海马神经元进行原代培养。用钙绿色-1荧光团加载细胞。采用Argus系统进行Ca（2+）显像和分析。结果10-100 nM BPA可引起N-甲基-D-天冬氨酸（NMDA）反应神经元胞内Ca（2+）浓度的短暂升高。钙（2+）瞬变发生在BPA应用后30秒内。在10 nM和100 nM BPA应用后，BPA响应神经元的比例分别为总NMDA响应神经元的9.6%和8.5%。用Ca（2+）通道阻断剂thapsigargin和nifedipine预处理神经元，BPA反应神经元的比例分别显著降低至0.7%和3.7%。用雌激素受体拮抗剂ICI 182，780处理神经元，也显著降低BPA反应神经元的比例至1.1%。结论低剂量BPA可通过激活雌激素受体等非基因组途径快速驱动钙信号系统。
OBJECTIVES Bisphenol A (BPA) is a typical endocrine disrupter. We investigated the mechanisms of rapid Ca(2+) signaling induced by a low dose BPA application in cultured hippocampal neurons. MATERIALS AND METHODS The primary culture of hippocampal neurons were prepared from postnatal 3 to 5-day-old rats. Cells were loaded with Calcium Green-1 fluorophore. Ca(2+) imaging and analysis were performed by Argus system. RESULTS The application of BPA at 10-100 nM induced a transient increase in the intracellular Ca(2+) of N-methyl-D-aspartate (NMDA)-responsive neurons. The Ca(2+) transient occurred within 30 sec after the BPA application. The proportion of BPA-responsive neurons was 9.6 % and 8.5 % of the total NMDA-responsive neurons, respectively, upon 10 nM and 100 nM BPA application. The pre-treatment of neurons with Ca(2+) channel blockers, thapsigargin and nifedipine, considerably decreased the proportion of BPA-responsive neurons to 0.7 % and 3.7%, respectively. The treatment of neurons with an antagonist of estrogen receptor, ICI 182,780, also significantly decreased the proportion of BPA-responsive neurons down to 1.1 %. CONCLUSION These results suggest that a low dose BPA application rapidly drives the Ca(2+) signaling system via activation of non-genomic pathway including estrogen receptors.