双酚A促进海马神经元树突发育并改变RhoA和Rac1/Cdc42的表达  

Bisphenol A Promotes Dendritic Development and Changes the Expressions of RhoA and Rac1/Cdc42 of Hippocampal Neurons

作　　者：张广侠[1] 徐晓虹[1] 陈蕾[1] 陆阳[1] 杨艳玲[1] 董芳妮[1] 

机构地区：[1]浙江师范大学化学与生命科学学院,浙江金华321004

出　　处：《生物物理学报》2013年第10期759-768,共10页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(81172627;30872087);浙江省自然科学基金重点项目(Z2090955)~~

摘　　要：双酚A(bisphenol A,BPA),是一种广泛用于塑料生产的环境内分泌干扰物,其对脑发育的不利影响已引起高度关注。为探讨BPA暴露对树突形态发育的影响及其分子机制,将体外培养6 d的新生海马神经元BPA(10和100 nmol/L)或17β-雌二醇(17β-E2,10 nmol/L)暴露24 h后,发现树突分支总长度显著增加,树突丝运动性及树突丝密度提高,同时增加F-actin表达,这些影响可被雌激素受体阻断剂ICI182780、非竞争性N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体拮抗剂MK-801和MEK1/2抑制剂U0126抑制。此外,BPA(100 nmol/L)暴露上调Rac1/Cdc42却下调RhoA的表达,此效应可被ICI182780完全消除,被U0126部分抑制。以上结果提示,BPA可通过雌激素受体介导的ERK1/2通路改变树突发育的上游调控分子,从而影响海马神经元树突的形态发育。Bisphenol A （BPA）, an environmental endocrine disruptor widely used in plastic production, has attracted high attention to its adverse effects on brain developmental process. The purpose of the study was to investigate the effects of exposure to BPA for 24 h on dendritic morphological development and the underlying mechanisms. The results demonstrated that cultured hippocampal neurons exposed to BPA （10, 100 nmol/L） or 1713-estradiol （17^-E2, 10 nmol/L） for 24 h significantly increased the total length of dendrite, motility and density of dendritic filopodia, as well as the expression of F-actin （filamentous actin）. These changes were suppressed by an ERs antagonist ICI182780, a non-competitive NMDA receptor antagonist MK-801, and a mitogen-activated ERK1/2-activating kinase （MEKI/2） inhibitor U0126. Furthermore, exposure to BPA （100 nmol/L） promoted the expression of Rac1/Cdc42 but inhibited that of RhoA, which were completely blocked by ICI182780, and partially suppressed by U0126. The results reveal that BPA changes upstream regulatory molecules of dendritic development through ERKI/2 signaling pathway mediated by estrogen receptor, and then affects the development of dendritic morphology in hippocampus neurons.

关 键 词：双酚A 海马神经元 树突形态发育 RhoA和Rac1 CDC42 

分 类 号：R992[医药卫生—毒理学]