慢性复合应激致老年小鼠学习记忆损伤及机制研究  

The effect of chronic stress on learning and memory impairment in old mice and its related mechanisms

作　　者：程娟[1] 王涛涛[1] 唐伟[1] 姚余有[1] 

机构地区：[1]安徽医科大学公共卫生学院,合肥230032

出　　处：《安徽医科大学学报》2013年第12期1466-1469,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1208085MH145);安徽高校省级自然科学研究项目(编号:KJ2011Z161)

摘　　要：目的探讨慢性复合应激对老年小鼠学习记忆能力的影响及可能机制。方法以老年小鼠为研究对象,实验分成应激组和对照组。采用Morris水迷宫试验观察慢性应激对老年小鼠学习记忆的影响;通过HE染色观察海马CA3区神经元病理组织形态;采用Western blot法检测小鼠海马β位淀粉样前体蛋白裂解酶1(BACE1)和β淀粉样蛋白1-42(Aβ1-42)的表达量;运用ELISA法检测血清皮质酮(CORT)含量。结果与对照组相比,实验组老年小鼠逃避潜伏期和游泳距离延长(P<0.01);CA3区海马神经元数目明显减少(P<0.01),排列疏松紊乱,脱失现象明显,核固缩,浓染;海马Aβ1-42和BACE1蛋白的表达量升高(P<0.01);血清CORT浓度升高(P<0.01)。结论慢性应激可导致老年小鼠学习记忆能力下降和海马组织损伤,其机制可能与慢性应激引起老年小鼠BACE1升高,促进Aβ1-42生成有关。Objective To determine whether chronic stress could potentiate learning and memory impairment in old mice, and, if so, what the underlying mechanism is. Methods Sixty male mice were divided randomly into control group and chronic stress group. Mice in stress group were stressed everyday by one of the stressors including cold exposure, restraint, level shake and so on. The ability of learning and memory was determined by Morris water maze test, and the histopathologic changes in CA3 field of the hippocampus were examined under a light microscope. Serum corticosterone level was determined by enzyme-linked immunosorbent assay. Western blot was performed to determine the expression of β-site amyloid precursor protein-cleaving enzyme 1 and Aβ1-42 in hippocampus of the brain. Results Compared with the control group, the results showed that chronic stress could increase the escape latency and swimming distance of old mice during training session in the Morris water maze test. The neuropathological changes were characterized by the decreased neuron number, soma shrinkage and condensation, or nuclear pyknosis in the CA3 field of hippocampus in the stress group. On the other hand, the expression of Aβ1-42 and BACE1 protein in hippocampus were increased, as well as the serum corticosterone concentration in the stress group. Conclusion Chronic stress can potentiate learning and memory impairment and pathological damage in CA3 field of the hippocampus in old mice, which may be related to chronic stress up-regulated the levels of BACE1 and Aβ1-42 mediated by corticosterone.

关 键 词：慢性应激 海马 Β淀粉样蛋白 皮质酮 学习记忆 

分 类 号：R338.64[医药卫生—人体生理学]