运动激活PGC-1a/FNDC5/BDNF通路延缓APP/PS1小鼠病理进程的机制研究

The Mechanism of Treadmill Exercise Activating PGC-1a/FNDC5/BDNF Pathway Delaying the Pathological Process of APP/PS1 Mice

探讨PGC-1a/FNDC5/BDNF信号通路在运动改善APP/PS1小鼠认知功能障碍中的作用机制。选用12只4月龄APPswe/PS1转基因雄性小鼠和12只同窝野生型小鼠,随机分AD对照组(AD-C,n=6)、AD运动组(AD-E,n=6)、野生对照组(WT-C,n=6)和野生运动组(WT-E,n=6)。WT-C组和ADC组小鼠安静饲养,WT-E组和AD-E组进行10周中等强度跑台运动干预。采用Western blot法检测实验小鼠海马PGC-1a、FNDC5、BDNF和Aβ蛋白表达情况。结果表明:与AD-C组小鼠相比,AD-E组小鼠海马内Aβ蛋白表达水平显著下(P<0.01),PGC-1a蛋白表达水平显著上升(P<0.01),FNDC5蛋白表达水平显著上升(P<0.01),BDNF蛋白表达显著上升(P<0.01),Aβ蛋白含量显著下降(P<0.01)。由此得到如下结论:长期中等强度的有氧运动激活APP/PS1小鼠海马PGC-1a/FNDC5/BDNF信号通路,降低海马区Aβ蛋白表达,改善APP/PS1小鼠空间学习记忆能力。

objective:to explore the mechanism of exercise-induced PGC-1a/FNDC5/BDNF signaling pathway in cognitive impairment in APP/PS1 mice.Methods:twelve 4-month-old male APPswe/PS1 transgenic mice and 12 littermates of wild-type mice were selected,and randomly divided into AD control group(AD-C,N=6),AD exercise group(AD-E,N=6),wild control group(WT-C,N=6)and wild exercise group(WT-E,N=6).Mice in WT-C and AD-C groups were reared quietly,and mice in WT-E and AD-E groups were subjected to 10-week moderate intensity treadmill exercise intervention.Western blot was used to detect the expression of PGC-1a,FNDC5,BDNF and Aβprotein in the hippocampus of mice.Results:compared with AD-C group,in AD-E group,the expression level of Aβprotein was significantly decreased(P<0.01),the expression level of PGC-1a protein was significantly increased(P<0.01),and the expression level of FNDC5 protein was significantly increased(P<0.01),the expression of BDNF protein was significantly increased(P<0.01),while the content of AΒprotein was significantly decreased(P<0.01).Conclusion:long-term moderate intensity aerobic exercise can activate PGC-1A/FNDC5/BDNF signaling pathway in hippocampus of APP/PS1 mice,decrease the expression of Aβprotein in hippocampus,and improve the ability of spatial learning and memory of APP/PS1 mice.