Effects Of Full-cycle Aerobic Exercise On Cognitive Function And Hippocampal Autophagy Activity In Mice Of Different Ages

Objective: A full-cycle aerobic exercise intervention experiment was designed to explore the effects of aerobic exercise on cognitive function and hippocampal autophagy activity in mice of different ages,and to analyze the role of autophagy in the effect of aerobic exercise on cognitive function in mice of different ages.Methods: Ninety 3-week-old male C57BL/6 mice were randomly and equally divided into aerobic exercise(E)and quiet control(C)groups.group E mice were subjected to aerobic running table exercise intervention at 75% VO2 max from 1 month of age,once every other day for 50 min/time.Fifteen mice from both groups were randomly selected at 3 months,12 months and 20 months of age,respectively,and were subjected to the water maze MWM and the open field test OFT to evaluate their spatial learning ability and adaptability to novel environments.The expression of LC3,beclin1 and its upstream SIRT1 and FOXO1 proteins in the hippocampus was measured by Western blot.The expression of ubiquitinated proteins in the hippocampus was measured by immunohistochemical staining(IHC)and the integral optical density(IOD)values were calculated.The data were processed using SPSS16.0 statistical software,and one-way ANOVA was used to test the significance of the data between groups at p<0.05.The SNK-q test was used for two-way comparison between different age groups in Group C at α=0.05.Results:(1)In the positioning navigation test five days before the water maze experiment,on the second day,the incubation period of mice in the 12-month-old exercise group was significantly lower than that in the control group(p<0.05).On day 3,the incubation period of mice in the 12-month-old and 20-month-old exercise groups was significantly lower than that of the control group of the same age(p<0.05).p<0.01)。 On the 4th and 5th days,the incubation period of mice in the exercise group of all ages was significantly lower than that of the control group of the same age(p<0.05).p<0.01)。 In the space exploration experiment on day 6,the time of mice in the quadrant of the original platform and the number of times they crossed the position of the original platform were significantly higher than those of the control group of the same age(p<0.05).(2)In the open field experiment,the number of crawling grids,the number of upright explorations and the activity time of the central area in the open field of mice decreased with age.Compared with the control group of the same age,the number of crawling grids,the number of upright explorations and the activity time in the central area were significantly increased in the exercise group(p<0.05).(3)Through the pair-by-pair comparison between the control group and different age groups,it was found that with the increase of age,the ratio of hippocampal autophagy labeled protein LC3II/LC3 I and the expression level of beclin1 protein in mice decreased significantly(p<0.05);(4)Compared with the control group of the same age,the ratio of hippocampal autophagy marker protein LC3II/LC3 I and the expression level of beclin1 protein in mice aged 12 months and 20 months were significantly increased(p<0.05).Exercise tended to inhibit hippocampal autophagy activity in 3-month-old mice,but there was no statistically significant difference(p>0.05).(5)Aerobic exercise had a significant promoting effect on the expression of hippocampal autophagy upstream activator SIRT1 and FOXO1 in mice of all ages(p<0.05).Conclusions:(1)The cognitive function(learning and memory ability,exploration ability,and adaptability to new environments)of mice decreased with age;(2)Aerobic exercise promoted the cognitive function of young mice and delayed the age-increasing decline of cognitive function in middle-aged and elderly mice;(3)The protective effect of aerobic exercise on cognitive function in elderly mice was related to the activation of hippocampal autophagy by exercise,but autophagy activity did not play a key role in promoting cognitive development in young mice by aerobic exercise;(4)SIRT1/FOXO1 signaling pathway may play an important role in aerobic exercise to activate autophagy activity in elderly mice,but it does not play a leading role in regulating hippocampal autophagy activity in young mice.