Effects Of Exercise On The Spinophilin-Immunoreactive Spine Number In CA1?CA3 And DG Of Hippocampus In The APP/PS1 Transgenic Mice

Objective: Alzheimer's Disease(AD)is a progressive neurodegenerative disease which will lead to cognitive impairment of the brain.However,up to now there has been no effective treatment for AD.It has been shown that running exercise is a potentially beneficial therapy for AD.This thesis studied the number of dendritic spine in male APP/PS1 transgenic AD mice and examined the influence of running excise on the dendritic spines in the hippocampus of male APP/PS1 transgenic AD mice.Methods: The 12-month-old male APP/PS1 transgenetic mice were randomly divided into positive control group(PG,n = 15)and running group(RG,n = 15).Concurrently,the wild-type mice with of the same age were assigned to negative control group(NG,n = 15).The mice in the running group were adapted to treadmill running for twenty minutes every day,five days each week and for lasting four months.The running velocity increased from 5 m/min to 10 m/min during the first two weeks and then was kept at 10 m/min until treadmill running exercise was finished at the end of the 4th month.Spatial learning ability and memory ability were evaluated using the Morris water maze after the last running exercise session.Later on,each group samples five mice randomly.Using the immunohistochemical method and the stereological method to evaluate the number of spinophilin-immunoreactive(Sp-ir)spines in the hippocampus of each mouse.Results: 1.After four-month's running exercise,in the hidden platform task,mice in the running exercise group and mice in the negative control group could find the platform more easily than mice in the positive control group.The escape latency time of mice in the positive control group was distinctly longer than that of mice in the negative control group(P = 0.002),while the escape latency time of mice in the running group was sharply shorter than that of mice in the positive control group(P = 0.016).In the probe trial task,the motion trails of mice in the running exercise group were much similar to the motion trails of mice in the negative control group,both of which lied in the original quadrant.The platform crossing times in the target quadrant of mice in the positive control group were substantially less than that of mice in the negative control group(P < 0.001),while the platform crossing times in the target quadrant of mice in the running group were apparently more than those of mice in the positive control group(P = 0.010).The time spending in the target quadrant of mice in the positive control group was evidently shorter than that of mice in the negative control group(P = 0.025),while the time spending in the target quadrant of mice in the running group was significantly longer than that of mice in the positive control group(P = 0.029).The swimming paths in the target quadrant of mice in the positive control group were distinctly less than those of mice in the negative control group(P = 0.040),while the time spending in the target quadrant of mice in the running group was evidently more than that of mice in the positive control group(P = 0.019).2.The stereological results showed that the density of the dendritic spines in the CA1,CA3 and DG of mice in the running group was significantly increased compared with that of mice in the positive control group(P < 0.01,P < 0.01,P < 0.01).3.Meanwhile,the total number of the dendritic spines in the CA1,CA3 and DG of mice in the running group was significantly increased in comparison with that of mice in the positive control group(P < 0.01,P < 0.05,P < 0.05).Conclusions: 1.The results of the Morris water maze test in this study indicated that exercise had positive effect on the spatial learning and memory ability of AD.2.The density and the total number of the Sp-ir spines in the CA1,CA3 and DG of the hippocampus in the APP/PS1 mice were decreased,which might be one of the most important neurobiological bases in the pathological process of AD.Yet the running exercise had increased the Sp-ir spines in the hippocampus in the APP/PS1 mice.Our data suggested that the protective effects of running exercise on the spatial learning and memory abilities of APP/PS1 mice might be related to the protective effects of running exercise on the dendritic spines in the hippocampus of APP/PS1 mice.