α-分泌酶ADAM10对APP转基因小鼠情绪和学习行为的影响  

Influence of α-secreatase ADAM10 on behavior of APP transgenic mice

作　　者：张玲[1] 林燕 

机构地区：[1]东南大学附属中大医院神经内科,南京210009 [2]德国美茵茨大学生物系

出　　处：《卒中与神经疾病》2007年第5期283-285,308,共4页Stroke and Nervous Diseases

摘　　要：目的探讨α-分泌酶ADAM10对阿尔茨海默病发生的作用。方法采用开场实验、高架十字迷宫和水迷宫实验测试并比较APP转基因小鼠和APP/ADAM10双转基因小鼠的行为学差异。结果与对照组小鼠相比,APP转基因小鼠焦虑性增高,自主活动力减弱,空间学习记忆力下降,差异有显著性(P<0.05);而APP/ADAM10双转基因小鼠各种行为和对照组相比无显著性差异(P>0.05)。结论α-分泌酶ADAM10能显著改善小鼠的情绪,提高APP转基因小鼠的自主活动力和学习、记忆能力,开发激活AD-AM10酶活性的药物或者在神经细胞表达ADAM10可望成为治疗阿尔茨海默病的新途径。Objective To investigate the influence of ADAM10 （a disintegrin and metalloprotease 10） on Alzheimer＇s disease （AD） using APP transgenic and APP/ADAM10 double transgenic mice as models. Methods APP transgenic,APP/ADAM10 double transgenic and wide type control mice were subjected to various behavioral tests including open field, elevated plus maze, and Morris water maze. Results In open field test, APP transgenic mice exhibited less motor activity, more anxiety （one way ANOVA, F = 38. 92, P〈0. 05） compared with wide type non-transgenic mice. In elevated plus-maze, APP transgenic mice showed less exploration in open arms （one way ANOVA, F = 290. 3, P〈0. 05）. In Morris water maze, APP transgenic mice showed spatial learning and memory deficits, compared with wide type non-transgenic mice （one way ANOVA, F = 6. 35, P〈0. 05）. While similar to that of wide type mice, APP/ADAM10 double transgenic mice showed restored learning and memory ability, less anxiety and more exploration compared with APP transgenic mice. Conclusions The results showed that neuronal overexpression of ADAM10 functionally increased explorative activity and alleviated anxiety and cognitive deficits, suggesting activation of ADAM10 as a promising therapeutic target in AD.

关 键 词：阿尔茨海默症 APP ADAM10行为学 

分 类 号：R743[医药卫生—神经病学与精神病学]