The Role Of AMPK In The Regulation Of Autophagy In Hippocampus And Learning And Memory By Exercise In Aged Mice's

Objectives:Investigate the role of AMPK in the regulation of autophagy by exercise in aged mice's hippocampus,in order to provides a scientific basis for the elderly to delay brain aging through scientific exercise.Methods:Twenty-one healthy 16-moths old female ICR mice,completely randomized devided into control group?aerobic exercise group and aerobic exercise in combination with Compound C group.The number of every group was seven.The CON group didn't accept any form of exercise intervention,the EXE group and E+C group experimented with aerobic exercise for four weeks and followed by a five-day Morris Water Maze test which can indicate the ability of mice's learning and memory.The E+C group is intraperitoneal injected Compound C every four days.The western blot detected the expression of proteins of hippocampus in mice including LC3,Beclin1,ATG7,Parkin,AMPK and mTOR.Result:1.Effects which aerobic exercising and aerobic exercising in combination with Compound C exerted on the capability of learning and memory in aging miceOn the third day of the place navigation,compared with the CON group,the escape latency in the water maze experiment of the EXE group was significantly reduced with the progress of the experiment(P<0.001),and so dose the total distance(P<0.05);Compared with the EXE group,the escape latency in the water maze experiment of the E+C group was significantly increased with the progress of the experiment(P<0.05),And so dose the total distance(P<0.05).2.Effects which aerobic exercising and aerobic exercising in combination with Compound C exerted on the autophagy-related proteins in aging mice's hippocampusCompared with the CON group,the EXE group's autophagy-related proteins have a significant increased which includes LC3 ?,Beclin1,ATG7,Parkin(P<0.05,P<0.01,P<0.01,P<0.05),LC3 ?/LC3 ? have a significant increased(P<0.05);Compared with the EXE group,the E+C group's autophagy-related proteins have a significant reduced which includes Beclinl,ATG7,Parkin(P<0.05,P<0.05,P<0.01,P<0.01),LC3 ?/LC3 I have a significant reduced(P<0.05).Compared with the CON group,the phosphorylation level of AMPK(p-AMPK/AMPK)in the EXE group was significantly increased(P<0.01),the phosphorylation level of mTOR(p-mTOR/mTOR)in the EXE group was significant decrease(P<0.01);Compared with the EXE group,the phosphorylation level of AMPK(p-AMPK/AMPK)in the E+C group was significantly decrease(P<0.05).By contrasting the EXE group,the phosphorylation level of mTOR(p-mTOR/mTOR)in the EXE group was significant increased(P<0.01).Conclusions:1.Aerobic exercise activated hippocampus autophagy and improved cognitive function in aged mice.2.Compound C partially cancelled the activation of hippocampus autophagy and the improvement of learning and memory in aged mice after exercise.AMPK plays a key role in the activation of hippocampus autophagy and the improvement of learning and memory in aged mice.