发育期双酚A暴露通过Wnt信号通路影响海马齿状回区突触形成（英文）

Developmental bisphenol-A exposure affects hippocampal dentate gyrus area spine formation through Wnt / β-catenin signaling

目的探讨发育关键期双酚A(BPA)暴露对海马齿状回(DG)区突触形成和树突棘的影响及其机制。方法出生7 d的SD大鼠,腹腔注射BPA 50,250和500μg·kg-1·d-1,连续7 d。Golgi-Cox染色分析海马DG区树突棘密度和树突棘头形态大小,Western blotting检测β联蛋白,Wnt7a及Wnt5a蛋白表达。结果 BPA 50,250和500μg·kg-1组海马DG区树突棘密度依次为9.67±0.17,8.97±0.13,(8.71±0.15)/10μm,相对于正常对照组的(10.21±0.17)/10μm,BPA 50,250和500μg·kg-1·d-1组树突棘密度显著下降(P<0.05)。正常对照组树突棘头为(0.67±0.03)μm2,BPA 50,250和500μg·kg-1组树突棘头依次为0.53±0.03,0.51±0.03和(0.50±0.03)μm2,显著低于正常对照组(P<0.05)。BPA 50,250和500μg·kg-1·d-1组磷酸化的β联蛋白占总体β联蛋白的百分比分别提高了18.28%,32.22%和57.01%,而Wnt7a表达显著降低(P<0.05),Wnt5a表达显著提高(P<0.05)。结论在BPA所引起的突触形成和树突棘的损伤中,Wnt信号通路可能起关键作用。

OBJECTIVE To investigate the effects and its underlying mechanism of bisphenoI-A （BPA） exposure on spine and synapse formation in detate gyrus （DG） area of hippocampus during criti- cal developmental period. METHODS Sprague-Dawley（SD） rats were injected intraperitoneally with BPA （50,250 and 500 pg.kg-1 .d-1 -1） from postnatal day 7 （PND7） to PND14. Dendritic spine morphol- ogy in DG area was examined using Golgi-Cox staining method and determined with Image J software. Western blotting method was employed to test the Writ related proteins. RESULTS The spine density and the average spine head size in BPA exposed groups significantly decreased in a close-dependent manner when compared to control group（ P 〈 0.05）. Meanwhile, Wnt related proteins were affected dur- ing BPA exposure. Specifically, the percentage of phosphorylated β-catenin increased following BPA ex- posure （P 〈0.05）, whereas Wnt7a expression level was significantly decreased and Wnt5a expression level increased （P〈0.05）. CONCLUSION Wnt signaling pathway plays an important role in BPA-in- duced impairments in spine and synapse formation.