运动对SAMP8小鼠海马tau蛋白磷酸化的影响

Effects of exercise on the tau phosphorylation in hippocampus of SAMP8 mice

目的探讨运动对快速老化小鼠(senescence-accelerated mouse/prone 8,SAMP8)海马tau蛋白磷酸化的影响。方法3月龄快速老化(SAMP8)小鼠20只随机分分为跑笼运动组和模型对照组,每组10只。另外,选取体重相匹配的雄性3月龄抗快速老化(senescence-accelerated mouse/resistant 1,SAMR1)小鼠10只,作为正常对照组。跑笼运动组小鼠每周5次跑笼运动训练,模型对照组和正常对照组常规饲养。2个月后,采用免疫组化法检测小鼠海马CA1区总tau蛋白(T-tau)免疫阳性细胞表达,Western blotting法分析海马磷酸化tau蛋白(P-tau)的表达。结果与SAMR1正常对照组比较,SAMP8模型对照组海马CA1区可见部分神经元细胞变性、死亡,核浓缩,空泡变性;跑笼运动组偶有神经元细胞变性、死亡,大部分细胞形态正常。SAMP8模型对照组海马CA1区T-tau蛋白免疫阳性细胞表达较SAMR1正常对照组显著增高(P<0.01),SAMP8跑笼运动组较SAMP8模型对照组减低(P<0.05)。SAMP8模型对照组海马p-Tau蛋白表达较SAMR1正常对照组表达减低(P<0.01),较SAMP8跑笼运动组表达升高(P<0.01)。结论运动对SAMP8小鼠海马神经元变性有一定延缓作用,海马T-tau和P-tau蛋白水平降低可能是运动改善AD学习记忆功能的重要机制之一。

Objective To explore the effects of exercise on the tau phosphorylation in hippocampus of the senescence accelerated mouse prone 8(SAMP8).Methods Twenty 3-month old SAMP8 mice were randomly divided into the cage running exercise(RCE)group and model control(MC)group with 10 mice in each group,and male 3-month senescence accelerated mouse resistant 1(SAMR1)were selected into the normal control(NC)group.The mice in the cage running exercise group were trained five times a week,and the mice in the model control group and normal control group were routinely fed.After two weeks,the expression of the total tau protein(T-tau)in the hippocampus CA1 Region of mice was detected by immunohistochemistry,and the expression of phosphorylated tau protein(P-tau)in the hippocampus was analyzed by Western blotting method.Results Compared with the SAMR1 NC group,neuronal cell degeneration&death,pycnosis,vacuole degeneration were noted in CA1 Region of hippocampus of mice in the SAMP8 MC group,while occasional neuronal cell degeneration&death and almost normal cell morphology were noted in the RCE group.The expression of positive T-tau protein immune cells in CA1 Region of the hippocampus of mice in the SAMP8 MC group was significantly higher than that of the SAMR1NC group(P<0.01);and which in the SAMP8 REC group were significantly lower than that in the SAMP8 MC group(P<0.05).The expression of P-tau in hippocampus of mice in the SAMP8 MC group was lower than that in the SAMR1 NC group(P<0.01);and which was higher in the SAMP8 MC group than the SAMP8 REC group(P<0.01).Conclusion Exercise is capable of delaying hippocampal neuronal degeneration in the SAMP8 mice,and the decreased protein level of hippocampal T-tau and P-tau may be one of the important mechanisms by which exercise improves learning and memory functions in AD.