Based On The Gut Microbiota,the Effect Of Aerobic Exercise On Cognition And HDAC2 Protein In APP/PS1 Double-transgenic Mice Was Discussed

Objective: The etiology of Alzheimer’s disease(AD)is complex,and the incidence of Alzheimer’s disease increases with the aging process of society,which brings serious burden to families and society.The pathogenesis of AD is unclear and there is a lack of early diagnostic means,making it difficult for patients to get treatment at the early stage of the disease.Studies have found that gut microbiota and histone deacetylation are related to AD to a certain extent.Overexpression of histone deacetylase in the brain can cause cognitive impairment.Gut microbiota and its products can inhibit the degree of histone deacetylation in the brain to a certain extent through brain-gut axis.According to studies,exercise can improve the learning and cognitive function of APP/PS1 mice,and play an independent role in the regulation and balance of gut microbiota.Therefore,APP/PS1 double transgenic mice were selected as the research objects in this study to explore the effect of exercise on brain histone deacetylation by regulating gut microbiota,hoping to provide theoretical and practical reference for the prevention and treatment of AD.Methods: Twenty-four APP/PS1 double transgenic mice were randomly divided into two groups: model control group(APC group)and model exercise group(APE group).Twenty-four C57BL/6 ordinary mice were randomly divided into two groups:wild control group(WTC group)and wild exercise group(WTE group).Each group had 12 animals.They were put on treadmill exercise for 10 weeks.After the intervention,the 6-day Morris water maze experiment was conducted to evaluate the learning and memory ability and spatial exploration ability of each group of mice.After 12 hours of water fasting,mice were anesthetized by intraperitoneal injection of3ml/kg 10% chloral hydrate.Hippocampal tissue was isolated on ice,and 6 mice were taken from each group for Western Blot detection.The other mice in each group received heart perfusion,and the whole brain was taken for embedding for HE staining and immunohistochemistry.Results:(1)Results of positioning navigation experiment: the escape latency of mice in each group was significantly shortened,APC group> APE Group t>WTC group >WTE group;Space exploration experiment: the number of mice in each group crossing the platform was WTE group>WTC group > APE Group;>APC group.(2)HE staining results: Cells in CA1 region of hippocampus in WTC group were arranged neatly with high density;Compared with the WTC group,the cells in the hippocampal CA1 region of APC group were sparsely arranged,the gap was larger,the cell morphology was different,and a large number of cells died.Compared with APC group,APE group had more orderly cell arrangement,higher density,smaller cell space and fewer dead cells.(3)Immunohistochemical results: Compared with WTC group,there was a significant decrease in HDAC2 in WTE group(P< 0.05),APE group increased but no significant difference(P> 0.05)and significantly increased in APC group(P< 0.01).Compared with APC group,there was a significant decrease in all groups(P< 0.01).(4)Western Blot results: HDAC2: Compared with WTC group,APE group increased but not significantly(P>0.05),WTE group significantly decreased(P< 0.05).Compared with APC group,WTC group,WTE group and APE group all decreased,with significant difference(P< 0.01).PSD95: Compared with WTC group,the expression of WTE group increased significantly(P<0.01),APE group decreased but not significantly(P> 0.05)and significantly decreased in APC group(P< 0.01).Compared with APC group,there was a significant increase in all groups(P<0.01,P<0.05).(5)16Sr high-throughput sequencing results: At the phylum level,there was no significant difference in the abundance of intestinal flora among the mice in each group;at the family level: the abundance of Lachnospiraceae was the highest in the APC group,the lowest in the WTE group,and the lowest among the four groups.There was no significant difference in the abundance of Lachnospiraceae;from the perspective of subordination level: the abundance of Lachnospira in the APC group was the lowest,and the WTE,WTC,and APE groups were all higher than APC,and there were significant differences compared with the APC group.Conclusion:(1)10-week aerobic exercise intervention can effectively improve the cognition, learning and memory ability of APP/PS1 mice.(2)10 weeks of aerobic exercise can reduce the level of HDAC2 in the hippocampus of APP/PS1 mice,inhibit the level of histone deacetylation,increase the level of PSD95,and improve the cognitive ability of the mice.(3)10-week aerobic exercise intervention can improve the diversity of gut microbiota, adjust the structure of gut microbiota,and repair the damaged intestinal mucosa.(4)After 10 weeks of aerobic exercise,the abundance of bacteria that can produce butyrate in gut microbiota increased,which may inhibit the expression of HDAC2 to a certain extent,reduce the level of histone deacetylation in the brain of mice,and improve the cognitive ability and learning and memory ability of mice.