文章摘要
周 景,朱 庆,刘景丽,钱文溢,高 蓉,王 军,肖 杭.围产期双酚A暴露对子代海马组织APP、Tau表达的影响[J].南京医科大学学报,2014,(7):909~914
围产期双酚A暴露对子代海马组织APP、Tau表达的影响
Effects of perinatal exposure to bisphenol A on APP and Tau expression in the hippocampus of offspring mice
投稿时间:2013-10-23  
DOI:10.7655/NYDXBNS20140711
中文关键词: 双酚A  淀粉样蛋白前体  微管相关蛋白
英文关键词: bisphenol A  amyloid precursor protein  microtubule-associated protein
基金项目:国家自然科学基金青年项目(81202230);国家自然科学基金(81273115);江苏省高校优势学科建设工程资助项目(CX09B_264Z);南京医科大学科技发展基金重点项目(2011NJMU275)
作者单位
周 景 南京医科大学公共卫生学院卫生毒理系,现代毒理教育部重点实验室,江苏 南京 210029 
朱 庆 南京医科大学公共卫生学院卫生毒理系,现代毒理教育部重点实验室,江苏 南京 210030 
刘景丽 南京医科大学公共卫生学院卫生毒理系,现代毒理教育部重点实验室,江苏 南京 210031 
钱文溢 南京医科大学公共卫生学院卫生毒理系,现代毒理教育部重点实验室,江苏 南京 210032 
高 蓉 南京医科大学公共卫生学院卫生毒理系,现代毒理教育部重点实验室,江苏 南京 210033 
王 军 南京医科大学公共卫生学院卫生毒理系,现代毒理教育部重点实验室,江苏 南京 210034 
肖 杭 南京医科大学公共卫生学院卫生毒理系,现代毒理教育部重点实验室,江苏 南京 210035 
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中文摘要:
      目的:观察F0代孕鼠围产期不同时期双酚A(bisphenol A,BPA)暴露对子代小鼠海马中淀粉样蛋白前体(amyloid precursor protein,APP)?微管相关蛋白(microtubule-associated protein,Tau)?磷酸化的Tau蛋白(p-Tau)的影响,探讨雌雄小鼠胎儿发育阶段BPA暴露的敏感期?方法:利用C57BL/6J胎鼠原代培养的海马神经元共孵BPA;F0代小鼠围产期皮下注射建立BPA暴露小鼠模型,根据不同暴露期分为4组,即对照组?胎儿期(P6-PND0)?哺乳期(PND0-PND21)?胎儿期和哺乳期联合暴露(P6-PND21),取其成年子代海马组织(8月龄)通过Western blot方法检测APP?Tau及p-Tau的表达量?结果:海马神经元细胞与不同浓度BPA共孵后,APP?Tau及p-Tau的表达均上调,呈剂量依赖性?BPA连续暴露后的子代小鼠中,雌性小鼠PND0-PND21组?P6-PND21组海马组织中APP?Tau及p-Tau表达增加,而雄性小鼠仅P6-PND21组3种蛋白的表达上调?结论:围产期BPA连续暴露可引起子代小鼠海马APP?Tau及p-Tau表达改变,从而可能引起神经损伤,而雌性小鼠相较于雄性小鼠可能对BPA引起的神经损伤更敏感?
英文摘要:
      Objective:To investigate the expression of amyloid precursor protein (APP),microtubule-associated protein (Tau),and phosphorylated Tau protein (p-Tau) of offspring mouse hippocampus after perinatal exposure of F0 mice to bisphenol A (BPA) on different stages,and identify critical windows for fetal development stage susceptibility to BPA exposure in male and female mice. Methods:Theprimary cultured hippocampus neurons of C57BL/6J fetal mice receiued with BPA;F0 mice received perinatal subcutaneous injection of BPA to establish the mouse BPA exposure model. Four groups were classified by different exposure stages,including the control,the fetus period (P6-PND0),the lactating period (PND0-PND21) and the combined exposure (P6-PND21) groups. The expressions of APP,p-Tau and Tau in offspring mouse(8-month-old) hippocampus were detected by Western blotting assays. Results:The expressions of APP,p-Tau and Tau protein of hippocampal neurons were increased in a dose dependent manner after incubation with varied concentrations of BPA. BPA obviously increased APP,p-Tau and Tau expressions in the PND0-PND21 and the P6-PND21 group of female mice;for the male mice,the three proteins' up-regulation was observed only in the P6-PND21 group. Conclusion:Continuous perinatal exposure to BPA could contribute to the up-regulation of APP,p-Tau and Tau,which might subsequently result in neuronal injury. Moreover,female mice are more susceptible to BPA exposure than male mice.
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