新皮质的微小损伤对阿尔茨海默病模型小鼠学习能力的影响

Impairment of Minimal Neocortical Injury on Learning Ability in Alzheimer Disease Model Mice

目的评估新皮质的微小损伤对阿尔茨海默病模型小鼠学习能力的影响。方法选取4~5月龄阿尔茨海默病模型雄性三转基因APP/PS1/tau小鼠(3xTg)和野生小鼠各20只,分为4组。应用脑立体定向仪,在皮质表面以下1 mm注入谷氨酸钠或生理盐水。通过Morris水迷宫检测空间学习能力;ELISA测定海马可溶性β-淀粉样蛋白(Aβ)水平;长时程增强(LTP)评估海马可塑性。结果 Morris水迷宫实验结果显示,与野生小鼠相比,3xTg小鼠学习成绩差(P <0.01);二次水迷宫测试结果显示,3xTg小鼠生理盐水对照组学习成绩明显改善,而3xTg小鼠谷氨酸钠注射组学习成绩无改善,2组存在统计学差异(P <0.05)。LTP、ELISA结果表明,3xTg小鼠生理盐水对照组在高频刺激后30 min内兴奋性突触后电位(fEPSP)的斜率显著高于3xTg小鼠谷氨酸钠注射组(P <0.05);3xTg小鼠谷氨酸钠注射组海马内可溶性Aβ显著增加(P <0.05)。结论新皮质的微小损伤可损害阿尔茨海默病模型小鼠学习能力。其导致海马内可溶性Aβ显著增加的机制有待进一步研究。

Objective To evaluate the effect of minimal neocortical injury on learning and memory in Alzheimer disease model mice.Methods Twenty 4-5 month 3 xTg AD mice were randomly divided into glutamate injection(3 xTg+G) group and saline injection(3 xTg+S) group;twenty wild type mice in the same background were in the group of(WT+G) and(WT+S). Sodium glutamate or saline was injected into the cortex 1 mm below the surface of the cortex by using brain stereotaxic apparatus for each group. Spatial learning ability was measured by Morris water maze,soluble Aβ level in hippocampus was measured by ELISA,and hippocampal plasticity was assessed by long-term potentiation(LTP). Results Morris water maze test showed that compared with wild mice,the learning performance of 3 xTg mice was worse(P < 0.01). Secondary water maze test showed that the learning performance of 3 xTg mice in saline control group was significantly improved,while 3 xTg mice in sodium glutamate injection group was not improved,and there was significant difference between the two groups(P < 0.05). The results of LTP showed that the slope of fEPSP in the saline control group of 3 xTg mice was significantly higher than that in the sodium glutamate injection group of 3 xTg mice within 30 minutes after high frequency stimulation(P < 0.05);ELISA showed the soluble Aβ in the hippocampus of 3 xTg mice was significantly increased in the sodium glutamate injection group(P <0.05). Conclusion Small damage to the neocortex may impair the learning ability of mice with Alzheimer disease. The mechanism of the significant increase of soluble Aβ in hippocampus remains to be further studied.