β淀粉样蛋白对大鼠学习记忆功能及tau蛋白异常磷酸化的影响

为了探讨β淀粉样蛋白对大鼠学习记忆功能和tau蛋白异常磷酸化的影响,本文在海马注射Aβ25-35建立阿尔茨海黙病(AD)大鼠模型的基础上,通过行为学检测、HE染色、免疫组化和免疫蛋白印迹技术对动物的学习能力、组织的病理改变和tau(pS202)、tau(pT231)和tau-5的表达情况进行了分析。在行为学检测中,Aβ注射组大鼠在穿梭箱实验中的主动回避次数和被动回避次数减少,失败次数增多,而在Morris水迷宫测试中的逃避潜伏期和游泳距离延长。HE染色显示Aβ注射组大鼠海马CA1、CA3、齿状回的神经细胞数目减少;而免疫组化和免疫印迹结果显示注射组tau(pS202)阳性细胞明显增加,tau(pS202)、tau(pT231)和tau-5蛋白表达增加。以上结果提示海马内注射Aβ25-35可引起大鼠学习记忆功能下降,可能与神经细胞减少,tau蛋白异常磷酸化增多有关。

EFFECTS OF AMYLOID-BETA PROTIEN ON LEARNING AND MEMORY ABILITY OF RATS AND ABNORMAL PHOSPHORYLATION OF TAU PROTEIN

To investigate the effects of amyloid-beta protein on the learning and memory ability of rats and abnormal phosphorylation of tau,Aβ25-35 was injected into hippocampus to establish the Alzheimer's Disease(AD)rat model.Learning and memory ability of AD rats were examined by shuttle box and Morris water maze.Neuropathology change of AD rats was observed by HE staining and immunohistochemical method,Western blotting were used to analyze the expressions of tau(pS202),tau(pT231)and tau-5,respectively.The Results showed that the times of active avoidance reaction and passive avoidance reaction decreased and the times of fail increased in Aβ25-35 treated rats when they were subjected to shuttle box test.Morris water maze test showed that the escape latency and swimming pathlength also prolonged.Moreover,a significant reduction in the numbers of neurons and the increase of tau(pS202)positive cells as well as the up-regulation of tau(pS202),tau(pT231)and tau-5 proteins in CA1,CA3 and dentate gyrus of Aβ-injected rats were also detected.These results suggest that hippocampal injection of Aβ25-35 can lead to the dysfunction of learning and memory,which may involve the decrease of the numbers of neurons and increase of abnormal phosphorylation of tau.