APP转基因拟痴呆小鼠模型脑内α-synuclein的增龄改变  

Expression of α-synuclein with aging in APP transgenic model of Alzhei mer's disease

作　　者：张兰[1] 于顺[2] 邢颖[1] 叶翠飞[1] 陈彪[2] 李林[1] 

机构地区：[1]首都医科大学宣武医院药物研究室 [2]首都医科大学宣武医院神经生物室,北京100053

出　　处：《中国病理生理杂志》2007年第12期2289-2294,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No30472184);国家重点基础研究发展计划"973"资助项目(NoG2003CB517104);北京市自然科学基金资助项目(No7072033)

摘　　要：目的:观察不同时程APP转基因拟痴呆小鼠脑内α-synuclein的改变,以探讨α-synuclein在AD发病中的作用。方法:拟AD动物模型为4月龄、10月龄和16月龄APP695V717I转基因小鼠;同背景同月龄C57BL/6J小鼠设为正常对照组。表达谱基因芯片、RT-PCR方法检测皮层、海马mRNA表达改变;Western blotting、免疫组化法检测蛋白表达的改变。结果:α-synuclein mRNA表达在不同时程APP转基因小鼠脑内均明显增多。α-sy-nuclein蛋白表达在早期4月龄APP转基因小鼠即显著上调,10月龄继续增多,16月龄继续上调并形成蛋白的异常聚集。结论:APP转基因小鼠脑内AD老年斑非Aβ主要成分α-synuclein表达明显增多,并随增龄不断加重,可能是模型小鼠学习记忆障碍及AD发病的重要因素。AIM ： To investigate the expression of α - synuclein in the brain of AD - like animal model at different age and to explore the pathology mechanism of α -synuclein in neural degeneration. METHODS： APP V717I transgenic （Tg） mouse model of Alzheimer＇s disease was observed at age of 4, 10 and 16 months. The Tg mice were randomly divided into 3 model groups （4, 10 and 16 months of age）. Control adopted the same age and background C57BL/6J mice. The mRNA expression of α - synuclein was measured by genechips and RT - PCR method. The protein of α - synuclein was detected by immuno - histochemistry and Western blotting. RESULTS ： The expression of α - synuclein mRNA increased significantly in hippocampus and cortex in Tg mice at age of 4 months, 10 months and 16 months compared with age matched controls. The production of α - synuclein protein also increased significantly in hippocampus and cortex in Tg mice at 3 groups. With aging, α - synuclein expression was increased and aggregated in Tg mice. CONCLUSION： Overexpression and aggregation of α - synuclein in different age of APP transgenic mice may play a key role in learning - memory deficit and the pathology of Alzheimer＇s disease, aging, and neural degeneration.

关 键 词：阿尔茨海默病 APP转基因小鼠 突触核蛋白 

分 类 号：R363[医药卫生—病理学]