| Objective: To study whether aerobic exercise for 8-weeks can decrease the deposition ofβ-amyloid peptide(Aβ)and improve the learning and memory ability and cognitive function of Alzheimer’s Disease(AD)mice by affecting the hippocampal Insulin/AKT/IDE pathway of AD mice.Methods: Sixty-four 12-week-old male C57BL/6j mice were randomly divided into the control group,the exercise group,the model group and the exercise model group with 16 mice in each group.The mice in the control group and the exercise group were intraperitoneally injected daily with 0.9% sodium chloride;The mice in the model group and the exercise model group were intraperitoneally injected daily with D-galactose(80mg/kg/day)combined with aluminium trichloride(5mg/kg/day)for continuous 8 weeks,to establish the AD Models.The mice in the exercise group and the model group performed the treadmill exercise at the same time,five times a week for 60 minutes each time.The mice began to run at 18 o’clock every day.First,the mice moved at a speed of 12m/min for 15 minutes,then,at a speed of 15m/min for 45 minutes.After the exercise intervention,the Y-Maze and the Morris water maze were used to detect the behavioral indicators to observe the situation of modeling.Aβ deposition and senile plaques were detected by Immunohistochemistry.The expression of insulin,AKT and IDE protein in hippocampus was detected by Western Blot methods.SPSS22.0 was used for statistical analysis,using one-way Anova,independent-sample T test for significant differences between groups.Results: 1.Learning and Memory Behavior Test: in Y-Maze Test,the total number of arm entry in model group was significantly lower than that in control group and exercise group(p < 0.05),and the total number of arm entry in exercise model group was significantly higher than that in model group(p < 0.05)The alternating reaction rate of the model group was significantly lower than that of the control group and the exercise group(p < 0.01).But the alternating reaction rate of the exercise model group was higher than that of the model group(p < 0.01).There was no significant difference in the total number of arm entry and the alternating reaction rate between the exercise group and the control group(p > 0.05).The incubation period of the model group was longer than that of the exercise group and the model group on the third day(p < 0.05).The incubation period of the model group on the fourth and fifth day was significantly longer than that of the control group,the exercise group and the model group(p < 0.05).There was no significant difference in the latent period between the model group and the control group(p > 0.05).2.The number of Aβ positive cells in the hippocampus of the model group was significantly higher than that in the control group(p < 0.01),and the number of Aβ positive cells in the exercise model group was significantly lower than that in the model group(p < 0.01);However,there was no significant difference between the model group and the control group(p > 0.05).3.Compared with the control group,the expression of insulin,Akt,P-AKT and IDE in model group was significantly lower than that in control group(p < 0.05);In the exercise model group,the expression of insulin,IDE,AKT and P-AKT was significantly increased(p < 0.05).4.Western Blot was used to detect the protein expression of insulin,AKT,P-AKT and IDE.The expression of insulin,AKT,P-AKT and IDE in model group was significantly lower than that in control group(p < 0.05);The protein expression of AKT and IDE in exercise model group was significantly higher than that in model group(p < 0.05),while the protein expression of insulin and P-AKT in exercise model group was increased,but there was no significant difference(p > 0.05);The expression of Aβ in the model group was significantly higher than that in the control group(p < 0.01),and the expression of Aβ in the model group was significantly lower than that in the model group(p < 0.05);Compared with the control group,the expression of insulin and IDE in the exercise group increased,but there was no significant difference(p > 0.05),and the expression of IR in the exercise group was almost the same,there was no statistical significance(p > 0.05).Conclusions:1.It was suggested that 8-week aerobic exercise could effectively prevent the impairment of spatial learning and working memory in AD model mice.2.The results of Aβdeposition histochemical analysis indicated that aerobic exercise decreased the deposition of Aβ in the hippocampus of AD mice at 8-weeks.3.Aerobic exercise up-regulated the expression of AKT,IDE protein in the hippocampus of AD mice,activated the Insulin/AKT/IDE pathway,accelerated the clearance of Aβ in the brain,and played a neuroprotective role. |
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