Hasegawa Yoshitaka, Ogiue-Ikeda Mari, Tanabe Nobuaki, Kimoto Tetsuya, Hojo Yasushi, Yamazaki Takeshi, Kawato Suguru
Department of Biophysics and Life Sciences, University of Tokyo, Tokyo, Japan.
Neuro Endocrinol Lett. 2013;34(2):129-34.
Low dose exposure to endocrine disrupters (environmental chemicals) may induce hormone-like effects on wildlife and humans. bisphenol A (BPA) might disturb the neuronal signaling regulated by endogenous estrogens. We investigated the rapid modulation effects of 10nM BPA, a typical endocrine disruptor, on long-term depression (LTD) of adult rat hippocampal slices.
LTD was induced by a transient perfusion of 30 µM NMDA for 3 min. And measured with multielectrode probes.
A 30 min perfusion of 10 nM BPA rapidly enhanced LTD in CA1, however, BPA suppressed LTD in dentate gyrus (DG). An ERRγ antagonist, 4-OH-tamoxifen, suppressed LTD in CA1 and DG. Inhibitor of estrogen receptor ICI 182,780 did not disturb BPA effects. On the other hand, tributyltin (TBT), another endocrine disruptor, did not have any effect on LTD in CA1 and DG.
ERRγ, but not estrogen receptors, is a high affinity BPA receptor in LTD processes, since the effect of BPA on LTD was suppressed by an ERRγ antagonist. A possible mechanisms of BPA-induced enhancement of LTD could be described with ERRγ, MAPK activation and phosphorylation of MMDA receptors.
低剂量接触内分泌干扰物(环境化学物质)可能会对野生动物和人类产生类激素效应。双酚A(BPA)可能会干扰内源性雌激素调节的神经元信号传导。我们研究了典型内分泌干扰物10nM BPA对成年大鼠海马切片长时程抑制(LTD)的快速调节作用。
通过短暂灌注30µM NMDA 3分钟诱导LTD,并使用多电极探针进行测量。
10nM BPA灌注30分钟可迅速增强CA1区的LTD,然而,BPA抑制了齿状回(DG)的LTD。ERRγ拮抗剂4-羟基他莫昔芬抑制了CA1区和DG区的LTD。雌激素受体抑制剂ICI 182,780并未干扰BPA的作用。另一方面,另一种内分泌干扰物三丁基锡(TBT)对CA1区和DG区的LTD没有任何影响。
在LTD过程中,ERRγ而非雌激素受体是高亲和力的BPA受体,因为ERRγ拮抗剂抑制了BPA对LTD的作用。BPA诱导LTD增强的一种可能机制可以用ERRγ、MAPK激活和MMDA受体磷酸化来描述。