| Objective: Alzheimer’s disease(AD)is a common and major age-related neurodegenerative disease affecting nearly 100 million people worldwide.According to statistics,more than 10 million people in China suffer from AD,and the incidence of AD among people over 65 years old is as high as 68.4%.Up to now,the pathogenesis of AD is still unclear,which leads to almost no useful drugs to treat AD.However,both clinical studies and animal experimental studies have shown that exercise can improve cognitive function and promote cognitive function,but there are few comparative studies on the effect of aerobic incremental load exercise,and the mechanism of its occurrence is still unclear.Based on the above situation,this study conducted aerobic incremental training for 8-month-old C57Bj-6J mice and APP/PS1 double transgenic Alzheimer’s disease model mice for 8 weeks,and observed and analyzed the effects of aerobic incremental load exercise on related indicators of learning and memory ability and related protein indicators of mice.To explore whether aerobic incremental load exercise can affect hippocampal neurongenesis of AD by inducing ARTN/ Irisin,and provide experimental and theoretical basis for improving cognitive dysfunction.Methods: A total of 74 C57 mice(n=40)and APP/PS1 mice(n=34)were adaptive reared for 1 week,and the mice were adaptive trained after the end of adaptive feeding.20 C57 mice and 14 APP/PS1 mice were selected according to the training of adaptation to running platform(as APP/PS1 mice were numbered by broken toes,some mice could not exercise normally after broken toes,so they were eliminated),and the remaining 40 qualified mice were divided into the following 4 groups: Normal control group(C group,n=10),APP/PS1 double transgenic quiet control group(M group,n=10),normal exercise group(CT group,n=10),APP/PS1 double transgenic exercise group(MT group,n=10)showed no significant difference in body weight between the observation groups.The CT group and MT group received aerobic incremental load training for 8weeks,and the program was as follows: the CT group and MT group received running speed of 10m/min for 30 min in week 1 and 2;In the third week and the fourth week,the running speed was increased to 15m/min and the duration was extended to 45 min.At the 5th and 6th week,the running speed remained unchanged at 15m/min,and the duration was extended for 60 min.During this period,the mice rested every 30 min for10min.Finally,at the 7th and 8th weeks,the speed was increased to 17m/min and the duration was 60 min,and the rest duration was 10 min every 30 min.The mice rested on Thursdays and Sundays in the 8th weeks.At week 4,week 6 and week 8,the effects of different exercise cycles on learning and cognitive ability of mice were observed.To observe and analyze spatial memory and learning in mice,the Morris Water Maze experiment was performed 24 hours after the end of the exercise intervention.After each Morris water maze test,a certain sample size was selected for animal sampling.The mice were dissected and the hippocampal tissue was removed from the brain,and the number of Neu N positive nerve cells in the dentate gyrus of the hippocampus was observed by immunohistochemistry.The expression levels of ARTN and Irisin proteins in hippocampus were detected by transcriptome sequencing.Results of Morris Water Maze experiment:(1)Positioning navigation experiment:In 4 weeks,6 weeks,8 weeks of navigation experimental observation,CT and MT group as the growth of the movement cycle load the rise in the average incubation period of mice with declining,the shortest was achieved at 8 weeks,the average incubation period of group C to fall,in 4 weeks and 6 weeks more gently,8 weeks,fell the most obvious.The overall mean incubation period of group M was not significantly changed.After the analysis of the average incubation period of each group on the same day,it was found that the average incubation period of group M was higher than that of CT group and MT group at three time nodes,and there was no significant difference in the average incubation period of each group on the first day(P>0.05).There was a significant difference on day 2.From day 2,the mean incubation period of the CT and MT groups was shorter than that of the M group(P<0.05).(2)Space exploration experiments: By means of three time points of space exploration experimental observation study found that compared with group C,group M platform,and the time and the number of cross platform all showed a trend of decline(P < 0.05),after aerobic increasing load training,CT and MT group of platform,and the time and the number of cross platform compared with M group tend to rise.(P < 0.05)2.Immunohistochemical test results of Neu N positive neurons in dentate gyrus of hippocampus: the staining of group C was deep,evenly distributed,and the cell distribution was reasonable and compact.However,in group M,the staining was shallow,and the nuclei were not clear and scattered with large spacing.Compared with M group,the number of Ne UN-positive neurons in MT group increased after 8 weeks of aerobic incremental load exercise,and the arrangement and combination of ne UN-positive neurons were more orderly,and there was a significant difference(P<0.05).The number,arrangement and distribution of CT group were more obvious(P<0.01).3.Expression results of ARTN and Irisin proteins in hippocampus: The m RNA expression level of ARTN/Irisin in hippocampus of mice in M group was the lowest.Compared with M group,the m RNA expression level of ARTN/Irisin in CT group and MT group was significantly increased at 4 weeks of exercise(P<0.05),and extremely significantly increased at 6weeks and 8 weeks of exercise(P<0.01).In addition,the expression level of ARTN/Irisin m RNA in CT group and MT group increased with the increase of exercise time,and the expression level was the highest at 8 weeks of exercise.Conclusions :(1)after 8 weeks of aerobic incremental exercise intervention,spatial learning and memory ability of APP/PS 1 double transgenic mice was improved,and cognitive decline was delayed to a certain extent.(2)Neu N positive neurons in the dentate gyrus of APP/PS 1 mice were up-regulated after 8 weeks of aerobic exercise,suggesting that regular aerobic exercise may enhance adult hippocampal neurogenesis and improve cognitive impairment in APP/PS 1 double transgenic mice.(3)The expression levels of ARTN and Irisin in hippocampus of APP/PS 1 mice were increased by aerobic incremental exercise,suggesting that the improvement of learning and memory ability of AD mice by aerobic incremental exercise may be related to the regulation of ARTN and Irisin. |
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