The Effect Of Exercise On The Cognitive Function Of Alzheimer's Disease (AD) And Its Mechanism

Part Ⅰ Effects of exercise on cognitive function and serum BDNF and IGF-1 in early AD patientsObjective:Give exercise intervention to early AD patients,determine the effect of exercise on cognitive function in early AD patients,and determine the changes of serum BDNF and IGF-1 in early AD patients.Methods: Administering 40 patients in early AD patients at least 3-4 times a week for one-year exercise intervention and a placebo intervention in the control group.After a year,cognitive function and daily living ability were assessed by the Neuropsychological Equivalence Scale(MMSE,Mo CA,ADAS-cog,CDR,and ADL);serum BDNF and IGF-1 were detected by ELISA in exercise intervention group and non-exercise intervention group.Results: 1.After 1 year of exercise intervention in the AD group and the normal elderly group,the cognitive decline was significantly delayed in the AD exercise intervention group compared with the AD non-exercise intervention group.However,there was no significant difference between the exercise group and the non-exercise group in the normal elderly.2.After 1 year of exercise intervention in the AD group and the normal elderly group,the AD exercise intervention group was compared with the AD non-exercise group,and there was no significant difference in daily living ability.There were no significant differences between the normal and non-exercise groups in the normal elderly.3.After exercise for 1 year in the AD group and the normal elderly group,the serum BDNF level in the AD exercise intervention group was significantly increased.There was no significant difference in serum IGF-1 levels between the two groups.However,there was no significant difference between the exercise group and the non-exercise group in the normal elderly.Conclusion: Exercise can delay the decline of cognitive function in early AD patients and increase the content of BDNF in serum,but it does not help to improve the daily living ability of patients with early AD.Part Ⅱ Effects of exercise on AD animal model--SAMP8 mice cognitive impairmentObjective: Based on clinical findings,exercise can improve the cognitive function of AD patients.The AD animal model—SAMP8 mice,is used to determine the effects of exercise on cognitive impairment in SAMP8 mice and the changes of the key transmitters in the brain.Methods: Healthy SAMP8 mice(6 months old)and SAMR1 mice(6 months old)were randomly divided into SAMP8 mouse run group,SAMP8 mouse control group,SAMR1 mouse run group,and SAMR1 mouse control group.The run group was given a 4-week exercise intervention.The expression of APP in hippocampus of SAMP8 mice and SAMR1 mice was determined by RT-PCR and Western Blot.The survival of hippocampus in SAMP8 mice and SAMR1 mice was determined by Nissle staining.Neuronal apoptosis in the hippocampus of SAMP8 mice and SAMR1 mice was detected by fluorescence staining.Morris water maze test was used to detect cognitive function in mice.Results:(1)The expression of APP RNA in hippocampus of SAMP8 mice was significantly higher than that of SAMR1 mice(P < 0.01).The expression of APP protein in hippocampus of SAMP8 mice was also significantly higher than that of SAMR1 mice(P < 0.01).(2)The results of Nissle staining showed that the expression of SAMP8 mice in hippocampal neurons(Nissle staining positive)was significantly lower than that in SAMR1 mice(P < 0.05);The results of fluorescent staining showed that the expression of neuronal apoptosis(Fluoro-JB positive)in hippocampus of SAMP8 mice was significantly higher than that of SAMR1 mice(P < 0.01).(3)Each group(n=8)including SAMP8 mice and SAMR1 mice was actively ran for 4 weeks.After 4 weeks,the Morris water maze test was continuously tested for 5 days.Compared with SAMR1 mice,the escape latency of SAMP8 mice was significantly prolonged.The difference was statistically significant(P < 0.001).Compared with SAMP8 control mice,the escape latency of SAMP8 run group was significantly shorter,and the difference was statistically significant(P < 0.001).Compared with SAMRl group,the swimming time in the SAMP8 group was significantly shorter in the platform quadrant,and the difference was statistically significant(P < 0.001).Compared with the SAMP8 control group,the swimming time of the SAMP8 run group was significantly increased in the platform quadrant,and the difference was statistically significant(P < 0.001).(4)After 4 weeks of exercise,the expression of APP protein in hippocampus of SAMP8 run group mice was significantly lower than that of SAMP8 control gruoup mice(P < 0.05).Furthermore,the expression of neuronal apoptosis(Fluoro-JB staining)in the hippocampus of SAMP8 run group mice was significantly lower than that of SAMP8 control group mice(P < 0.05).Conclusion: Exercise can improve the cognitive function of SAMP8 mice and reduce the expression of APP and neuronal apoptosis in the hippocampus of SAMP8 mice.Part Ⅲ The role of mi R-132 in exercise training on cognitive impairment in SAMP8 miceObjective : To clarify the role of mi R-132 in exercise training on cognitive impairment in SAMP8 miceMethods: Healthy SAMP8 mice(6 months old)and SAMR1 mice(6 months old)were randomly divided into SAMP8 mouse run group,SAMP8 mouse control group,SAMR1 mouse run group,and SAMR1 mouse control group.The run group was given a 4-week exercise intervention.The expression of mi R-132 in hippocampus of SAMP8 mice and SAMR1 mice was determined by q RT-PCR and in situ hybridization.Healthy SAMP8 mice were selected to inject mi R-NC,mi R-132-agomir or mi R-132-antagomir into bilateral hippocampal.These mice were given active exercise for 48 hours,and Morris water maze test was used to detect cognitive function in mice.Results:(1)The expression of mi R-132 in SAMP8 mice and their control SAMR1 mice was measured before exercise intervention: the expression of SAMP8 in hippocampus was significantly higher than that in SAMR1 mice.There was a statistically significant difference(P <0.01).4 weeks after exercise,the expression of mi R-132 in hippocampus of each group was determined by q RT-PCR.It was found that SAMP8 control mice were compared with SAMR1 control mice.The expression level increased significantly,and there was a statistically significant difference(P<0.01).The expression of SAMP8 run group was significantly lower than that of SAMP8 control mice.(P<0.05).At the same time,we also used in situ hybridization to measure the expression of mi R-132 in the hippocampus of each group,and found that the expression of SAMP8 control mice compared with SAMR1 control mice.Significantly increased,there was a statistically significant difference(P<0.01);the expression of SAMP8 run group was significantly lower than that of SAMP8 control mice,which was statistically significant(P <0.05).(2)Morris water maze test results showed that compared with SAMP8-mi R-NC mice,the escape latency of SAMP8-mi R-132-antagomir mice was significantly shortened,and the difference was statistically significant(P<0.01).The escape latency of SAMP8-mi R-132-agomir mice was significantly prolonged,and the difference was statistically significant(P<0.05).Compared with SAMP8-mi R-NC mice,SAMP8-mi R-132-antagomir mice significantly increased swimming time in the platform quadrant,the difference was statistically significant(P<0.001).The swimming time of SAMP8-mi R-132-agomir mice in the platform quadrant was significantly reduced,and the difference was statistically significant(P <0.001).Conclusion: The expression of mi R-132 in the hippocampus of SAMP8 mice after exercise intervention was significantly reduced.Injection of mi R-132 agonists in the hippocampus of SAMP8 mice aggravated cognitive impairment,whereas injection of mi R-132 antagonists improved cognitive function.mi R-132 may be a key molecule in the regulation of exercise intervention to improve the cognitive function of SAMP8 mice.