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

摘要

OBJECTIVE To investigate the effects and its underlying mechanis m of bisphenol-A (BPA)exposure on spine and synapse formation in detate gyrus (DG)area of hippoca mpus during criti-cal develop mental period.METHODS Sprague-Dawley(SD)rats were injected intraperitoneally with BPA (50,250 and 500 μg·kg -1·d -1 )fro m postnatal day 7 (PND7)to PND14.Dendritic spine morphol-ogy in DG area was exa mined using Golgi-Cox staining method and determined with I mage J software. Western blotting method was e mployed to test the Wnt related proteins.RESULTS The spine density and the average spine head size in BPA exposed groups significantly decreased in a dose-dependent manner when co mpared 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 i mportant role in BPA-in-duced i mpairments in spine and synapse formation.%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。