淀粉样蛋白前体/早老素1转基因小鼠大脑皮质内kinesin1介导的神经元轴浆运输障碍  

Kinesin1-mediated neuronal axoplasmic transport disorder in cerebral cortex of amyloid precursor protein/presenilin-1 transgenic mice

作　　者：王倩[1] 范文娟[1,2] 孙仪征 王来[1] 邓锦波[1] WANG Qian1, FAN Wen-juan1＇2, SUN Yi-zheng1, WANG Lai1, DENG Jin-bo(1. Institute of Neurobiology, College of Life Science, He＇ nan University, He＇ nan Kaifeng 475004, China ; 2. Molecular Medical Laboratory, Luohe Medical College, He＇ nan Luohe 462002, Chin)

机构地区：[1]河南大学生命科学学院,河南大学神经生物学研究所,河南开封475004 [2]漯河医学高等专科学校分子医学实验室,河南漯河462002

出　　处：《解剖学报》2018年第2期158-165,共8页Acta Anatomica Sinica

基　　金：河南省教育厅科学技术研究重点项目(12B180016)

摘　　要：目的探讨轴突运输蛋白,kinesin1和神经丝蛋白(SIM-312)在阿尔茨海默病(AD)发生、发展中的作用。方法出生后30~360 d淀粉样蛋白前体(APP)/早老素1(PS1)转基因小鼠(n=40)和野生型小鼠(n=40)用于此研究,利用免疫荧光染色和Western blotting技术检测上述两种小鼠大脑皮层内老年斑的沉积及星形胶质细胞的分布以及在大脑皮质发育过程中kinesin1和SIM-312阳性细胞个数及蛋白的表达变化。结果 APP/PS1转基因小鼠与正常对照组相比,β-淀粉样蛋白(Aβ)斑块增多,星形胶质细胞数目增多,神经元减少;而kinesin1阳性细胞的数量在APP/PS1转基因小鼠生长发育过程中减少,且在出生9月(P9M)之后与野生型小鼠之间差异存在着显著性(P<0.05);SIM-312标记的神经丝蛋白随着年龄的增长自P6M之后开始出现缠结现象。结论 Kinesin1和SIM-312的异常改变导致神经元中轴浆运输障碍以及AD的病理变化。Objective To understand the roles of axonal transport proteins,kinesin1 and SIM-312,in the pathogenesis and development of Alzheimer＇s disease. Methods Amyloid precursor protein（ APP）/presenilin-1（ PS1）transgenic mice（ n = 40） and wild type mice（ n = 40） from postnatal day 30 to postnatal day 360 were used in the study.Amyloid beta-peptides（ Aβ） plaques and astrocytes in cerebral cortex were visualized with immunofluorescent labeling and Western blotting. Results Compared with wild type mice,Aβ plaques and astrocytes increased in cerebral cortex of APP/PS1 mutant mice,especially after 9 months,with statistical significance. However,after 9 months,the number of kinesin1-positive cells decreased in APP/PS1 transgenic mice,and SIM-312 positive neurofilaments appeared tangled in the cerebral cortex of AD mice as well. Conclusion Abnormal kinesin1 and SIM-312 are involved in axonal transportation disorder in AD mice,suggesting they are the important pathogenic factors of AD.

关 键 词：阿尔茨海默病 轴浆运输障碍 神经丝蛋白 Kinesin1 免疫印迹法 小鼠 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]