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

Abstract

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 17β-estradiol(17β-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(MEK1/2) 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 ERK1/2 signaling pathway mediated by estrogen receptor,and then affects the development of dendritic morphology in hippocampus neurons.