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

doi:10.3969/j.issn.1006-7795.2020.03.014

首都医科大学学报 ›› 2020, Vol. 41 ›› Issue (3): 391-396.doi: 10.3969/j.issn.1006-7795.2020.03.014

• 中药有效成分治疗脑损伤 • 上一篇下一篇

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

杨翠翠, 包训杰, 张丽, 李雅莉, 李林, 张兰

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

收稿日期:2020-02-29 出版日期:2020-06-21 发布日期:2020-06-17
通讯作者: 张兰 E-mail:lanizhg@126.com
基金资助:
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）。

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

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

Received:2020-02-29 Online:2020-06-21 Published:2020-06-17
Supported by:
This study was supported by National Natural Science Foundation of China (81874351,81703729), Natural Science Foundation of Beijing (7164315),Beijing High-level Health and Technical Personal Plan (2014-2-014).

摘要/Abstract

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。

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

Abstract: 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 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.

Key words: Alzheimer's disease, cornel iridoid glycoside, APP/PS1/tau, synaptic protein

中图分类号:

R743

杨翠翠, 包训杰, 张丽, 李雅莉, 李林, 张兰. 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[J]. 首都医科大学学报, 2020, 41(3): 391-396.

Yang Cuicui, Bao Xunjie, Zhang Li, Li Yali, Li Lin, Zhang Lan. 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[J]. Journal of Capital Medical University, 2020, 41(3): 391-396.

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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

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