Effects Of Aerobic Exercise On Production And Metabolism Of A? In Brain Of APP/PS1/tau Mice

Objective: This study was aimed at observing the effects of 12 weeks of aerobic exercise on the occurrence and development of central A? formation and clearance in AD model APP/PS1/tau transgenic mice at different stages,and exploring the mechanism of aerobic exercise to alleviate pathological changes in AD.Methods:(1)Experimental groups: 2,6,9 and 12 months old APP/PS1/tau mice,2months old AS as the normal control group of this genus,6,9 and 12 months old mice were randomly divided into sedentary control group(AS)and aerobic exercise group(AE).Exercise plan: the AE groups ran for 12 weeks.Treadmill grade was 0 °,60min/d,5 d/w,and the load was 12m/min at the first 10 minutes and 15m/min at the last 50 minutes.(2)Immunofluorescence staining was used to detect the content of A?polymer.(3)The protein expressions of oligomeric beta-amyloid in cerebral cortex and hippocampus were detected by Dot blot.(4)Western blot was used to detect the protein expression of BACE1 and NEP in the cerebral cortex and hippocampus of mice in each group,and the protein expression of IDE in liver.Results:(1)There was no aggregation of A? in the cortex and hippocampus of the AS group at 2 months old,and only a small amount of scattered A? was found in the cortex and hippocampus of the AS group and the AE group at 6 months old with no deposition found.The cortex and hippocampus of the AS and AE groups showed obvious pathological A? deposition at the age of 9 and 12 months.Compared with AS group,the content of A? polymer in cortex and hippocampus of 9-month and12-month old mice was significantly decreased in AE group(P < 0.01).With the increasing of the age of the month,the A? polymer's content of APP/PS1/tau mice in cortical and hippocampal increased significantly(P < 0.01).(2)Compared with AS group,the content of oA? in cortex and hippocampus of mice aged 6,9 and 12 months were significantly reduced in AE group(P < 0.01).Compared with the AS group at 2 months of age,the content of cortex and hippocampus oA? in the AS group at 6,9 and 12 months of age were significantly increased with the increasing of the age(P < 0.01).(3)The protein expression of BACE1 in cortex and hippocampus in the AE group at 6 months old was significantly lower than that in the AS group at 6months old(P < 0.05 or P < 0.01),while the protein expression of both NEP in the cortex and hippocampus(P < 0.01)and the IDE in liver(P < 0.05)were significantly increased than those in AS group.Compared with the 9-month-old AE group,the BACE1 in cortex and hippocampus was significantly reduced(P < 0.01),while NEP expression in cortex and hippocampus was significantly increased(P < 0.01),and IDE protein expression in liver was also significantly increased(P < 0.05)in the AS group.Compared with the 12 months AS group,the BACE1 protein expression of cortex and hippocampus in the 12-month AE group was significantly reduced(P <0.01),while the NEP in cortex and hippocampus was significantly increased(P <0.01),and the IDE protein expression in liver was also significantly increased(P <0.01).Compared with the 2-month-old AS group,the 6,9 and 12 months AS group's protein expression of BACE1 in the cortex and hippocampus increased significantly(P < 0.01),while NEP in the cortex and hippocampus of the 6,9 and 12 months AS group decreased significantly(P < 0.05 or P < 0.01).Conclusion: In APP/PS1/tau transgenic mice at different times of 6,9 and 12 months,12 weeks regular aerobic exercise can obviously reduce the BACE1 protein expression in the brain,improve protein expression of the NEP in the brain and the IDE in the liver.These results show that reduced beta amyloid protein expression by aerobic exercise may be the mechanism of the symptoms alleviation of AD.