转基因小鼠脑组织中突触素和发动蛋白Ⅰ及衔接蛋白180表达的变化

Changes of expression of synaptophysin,dynamin Ⅰ and AP180 in brains of the mice with Swedish mutation of APP

目的探讨瑞典型淀粉样前体蛋白突变基因转基因小鼠脑组织中突触素(synaptophysin)、发动蛋白Ⅰ(dynamin Ⅰ)及衔接蛋白180(AP180)表达变化。方法选择6只瑞典型淀粉样前体蛋白突变基因转基因小鼠为转基因组,另选5只小鼠为对照组。采用免疫组织化学染色法检测小鼠海马及颞叶皮质synaptophysin、dynamin Ⅰ及AP180的表达,图像分析半定量;免疫组织化学双染法观察转基因小鼠脑组织中synaptophysin与β淀粉样蛋白(Aβ)_(1-42)在老年斑表达部位的关系。结果与对照组比较,转基因组小鼠脑组织齿状回分子层、海马CA1、CA3及内嗅区皮质各层synaptophysin平均灰度值明显增高(P<0.05,P<0.01);齿状回颗粒细胞、海马CA1锥体细胞及内嗅区皮质各层dynamin Ⅰ平均灰度值明显增高(P<0.05,P<0.01);齿状回分子层、海马CA4、CA1、内嗅区皮质各层及颞叶皮质Ⅱ～Ⅴ层AP180平均灰度值明显增高(P<0.05,P<0.01)。免疫组织化学双染显示转基因组小鼠老年斑内有synaptophysin和Aβ_(1-42)共同存在。结论转基因小鼠脑组织中synaptophysin、dynamin Ⅰ及AP180表达降低,提示出现不同程度突触丧失及突触囊泡回收功能缺陷,可能是该小鼠认知功能障碍的原因之一。

Objective To investigate protein expression of synaptophysin,dynamin Ⅰ and AP180 in brains of the transgenic mice carrying Swedish mutation of amyloid precursor protein（APP） 670/ 671（APPSWE）. Methods The protein expression of synaptophysin, dynamin Ⅰ and AP180 in brains of 6 transgenie mice with APPSWE and five age-matched controls was detected by immunohistochemical method. Results Compared with controls,the synaptophysin-like immunoreactivity in the molecular layer of dentate gyrus,hippocampal CA1 and CA3,entorhinal cortex of brains of mice with APPswE was decreased （P 〈 0. 05）, the dynamin Ⅰ -like immunoreaetivity was declined in granular cells of the dentate gyrus,pyramidal cells of the hippocampal CA1,and the neurons of the Ⅱ --Ⅴ layers of the entorhinal cortex （P 〈 0.05） ,the AP180-like immunoreactivity was de- creased in the molecular layer of dentate gyrus, hippocampal CA1 and CA4,entorhinal cortex and the Ⅱ --Ⅴ layers of the temporal cortex （P 〈 0.05）. Co-immunohistochemical staining of synap- tophysin and Aβ1-42 was shown in the senile plagues in brains of mouse with APPswE. Conclusions The decreased expression of synaptophysin, dynamin Ⅰ and AP180 in mouse brains with APPSWE may indicate reduced number of synapse and defect of synaptic vesicle endocytosis,which may be the mechanism resulting in cognitive deficit of APPswE mice.