7月龄及16月龄APP/PS1/tau三转基因小鼠脑内突触相关蛋白的变化及山茱萸环烯醚萜苷的影响  

Changes of synapse-related proteins in the brain of 7-month-old and 16-month-old APP/PS1/tau transgenic mice and the effects of cornel iridoid glycoside on the AD model

作　　者：杨翠翠[1] 包训杰 张丽[1] 李雅莉[1] 李林[1] 张兰[1] Yang Cuicui;Bao Xunjie;Zhang Li;Li Yali;Li Lin;Zhang Lan(Department of Pharmacy,Xuanwu Hospital,Capital Medical University,Beijing Engineering Research Center for Nerve System Drugs,Beijing Institute for Brain Disorders,Key Laboratory for Neurodegenerative Disease of Ministry of Education,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院药学部,北京市神经药物工程技术研究中心,北京脑重大疾病研究院神经变性病教育部重点实验室,北京100053

出　　处：《首都医科大学学报》2020年第3期391-396,共6页Journal of Capital Medical University

基　　金：国家自然科学基金(81874351,81703729);北京市自然科学基金(7164315);北京市高层次卫生技术人才计划(2014-2-014)。

摘　　要：目的探讨不同月龄APP/PS1/tau三转基因(3×Tg)小鼠脑内突触相关蛋白及其影响因素的变化,为选择合适时程的3×Tg小鼠进行阿尔茨海默病(Alzheimer’s disease,AD)研究提供参考数据;并且研究山茱萸环烯醚萜苷(cornel iridoid glycoside,CIG)对模型小鼠脑内突触相关蛋白的影响,从而明确其对不同月龄的模型动物的作用特点,为阐明CIG改善AD样认知障碍机制提供实验依据。方法 7月龄小鼠3×Tg小鼠给予200 mg/kg CIG至9月龄,16月龄3×Tg小鼠给予100或200 mg·kg-1·d-1 CIG至18月龄;采用新物体识别实验检测CIG对学习记忆的影响;采用Western blotting方法检测突触相关蛋白synapsin-1、synaptophysin和synaptotagmin的表达,淀粉样前体蛋白(amyloid precurson protein,APP)及相关代谢酶α分泌酶(recombinant a disintegrin and metalloprotease 10, ADAM10)、β分泌酶(β-site APP-cleaving enzyme 1, BACE1)、早老素1(presenilin-1,PS1)、胰岛素降解酶(insulin degrading enzyme, IDE)的表达,tau蛋白在pSer404及pSer199/202位点的磷酸化水平。结果 7月龄3×Tg模型小鼠与对照组小鼠相比,物体识别分辨指数无明显变化,主要突触相关蛋白synapsin-1、synaptophysin和synaptotagmin的表达没有差异,CIG给药未对3×Tg模型小鼠分辨指数及脑内突触相关蛋白产生影响;16月龄3×Tg小鼠物体识别分辨指数明显降低,synapsin-1在脑内表达水平均相比对照组下降,而给予CIG治疗后不仅能够提高转基因小鼠的分辨指数,而且明显提升synapsin-1的表达。7月龄3×Tg小鼠模型与对照组全长APP、ADAM10、BACE1、PS1、IDE及tau蛋白磷酸化水平比较,差异均无统计学意义(P>0.05)。结论突触相关蛋白在不同月龄3×Tg小鼠脑内表达差异较大,CIG对不同月龄3×Tg小鼠脑内突触相关蛋白的表达及认知功能存在不同作用特点。Objective To explore the changes of memory ability and synapse-related proteins along with their influencing factors in the brain of APP/PS1/tau(3×Tg)transgenic mice[JP+2]of 7 and 16-month old,and to study the effect of cornel iridoid glycoside(CIG)on synapse-associated proteins in the brain of model mice.Methods 3×Tg mice of 7-month-old and 16-month-old were both treated with CIG for 2 months.New object recognition test was used to detect the ability of learning and memory in 3×Tg mice.Western blotting was used to observe the expression of synapsin-1,synaptophysin,synaptotagmin,amyloid precurson protein(APP),recombinant a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),presenilin-1(PS1),insulin degrading enzyme(IDE),and tau phosphorylation at Thr212 and Thr217.Results Compared to control group,7-month-old 3×Tg mice had no change in the discrimination index,expression of synapsin-1,synaptophysin and synaptotagmin in cortex,while 16-month-old 3×Tg mice showed lower discrimination index and less expression of synapsin-1.After treatment,16-month-old 3×Tg mice showed higher discrimination index and more expression of synapsin-1.Compared to control group,7-month-old 3×Tg mice showed a similar level of APP,ADAM10,BACE1,PS1,and IDE in the brain.Conclusion Synapse-associated proteins are differentially expressed in the brains of 3×Tg mice at different ages.CIG has distinct effects on the expression of synapse-related proteins and memory ability in the brains of 3×Tg mice at different ages.

关 键 词：阿尔茨海默病 山茱萸环烯醚萜苷 APP/PS1/tau 突触相关蛋白 

分 类 号：R743[医药卫生—神经病学与精神病学]