| Objective: In this study,APP/PS1 transgenic mice and wild-type mice were used as research subjects,to explore the effects of 12 weeks moderate intensity treadmill exercise,observing whether exercise activated VEGF pathway in AD mice could improve the Aβ induced decrease in synapse related receptor expression.To explore whether exercise is involved in the activation of VEGF/VEGFR2 pathway in improving Aβ induced decrease in AMPA receptor GluR1 expression,in order to provide new ideas for exercise to prevent the occurrence and development of AD.Methods: Eighteen 13-week-old male APP/PS1 transgenic mice and Eighteen13-week-old male C57BL/6 mice were used in this study.APP/PS1 transgenic mice were randomly divided into AD Control group（ADC）and AD Exercise group（ADE）,with 9 mice in each group.Wild-type mice were randomly divided into wild-type Control group（WTC）and wild-type Exercise group（WTE）,with 9 mice in each group.Both WTE and ADE groups began to do treadmill exercise for a total of 12 weeks at the age of 13 weeks,Exercise program: five times a week,each 45 minutes.The Morris Water Maze test was conducted for 6 days at week 13 after the 12-week treadmill exercise.12 hours after the end of the water maze experiment,the mice were anesthetized with isoflurane and bilateral hippocampi were taken.The mean intensity of Aβ in the hippocampus of mice was detected by immunofluorescence assay;the mRNA expressions were detected by real-time PCR;Western blotting assay was used to detect the protein expression.Results:（1）In the positioning navigation experiment,the escape latencye of the ADC group,compared with the WTC group,increased significantly on day 3（P<0.05）,day 4（P<0.05）and day 5（P<0.01）,and the percentage of platform quadrant time of the ADC group decreased significantly on day 3（P<0.01）,day 4（P<0.01）and day 5（P<0.05）;After 12 treadmill exercise,compared with ADC group,the escape latency of ADE group was significantly decreased on day 4（P<0.05）and 5（P<0.05）,and the percentage of platform quadrant time of ADE group was significantly increased on day 4（P<0.05）and day 5（P<0.05）.In space exploration experiment,compared with WTC group,the times of crossing the platform（P<0.01）,the percentage of platform quadrant distance（P<0.05）and the percentage of platform quadrant time（P<0.05）were significantly reduced in the ADC group;After 12 weeks of treadmill exercise,the times of crossing the platform（P<0.05）,the percentage of platform quadrant distance（P<0.05）and the percentage of platform quadrant time（P<0.05）in the ADE group were significantly higher than in the ADC group.（2）The Aβ sedimentary area in the hippocampus of mice in the ADC group was significantly increased compared with the WTC group（P<0.01）,and the ADE group was significantly reduced compared with the ADC group（P<0.05）.（3）The mRNA level of VEGF and VEGFR2 in hippocampus of ADC group significantly lower than those of WTC group（P<0.05）;the mRNA level of VEGF and VEGFR2 in hippocampus of ADE group significantly higher than those of ADC group（P<0.05）;The protein level of VEGF and p-VEGFR2 in hippocampus of ADC group significantly lower than those of WTC group（P<0.05）;The protein level of VEGF and p-VEGFR2 in hippocampus of ADE group significantly higher than those of ADC group（P<0.05）;（4）The protein and mRNA expressions of CaN in the hippocampus of the mice in the ADC group were significantly higher than those in the WTC group（P<0.05）;the protein and mRNA expressions of CaN in the hippocampus of the mice in the ADE group were significantly lower than those in the ADC group（P<0.05）.Compared with the WTC group,the protein expression of cleaved caspase 3 in the hippocampus of the mice in the ADC group was significantly increased（P<0.05）.The protein expression of cleaved caspase3 in the hippocampus of the mice in the ADE group was significantly lower than that in the ADC group（P<0.05）.（5）The mRNA level（P<0.05）,protein level（P<0.05）and phosphorylation level（P<0.05）of GluR1 in hippocampus of ADC group significantly lower than those of WTC group;the mRNA level（P<0.05）,protein level（P<0.05）and phosphorylation level（P<0.05）of GluR1 in hippocampus of ADE group significantly higher than those of ADC group.Conclusion: Treadmill exercise may activate the VEGF/VEGFR2 pathway in the brain of APP/PS1 mice,thereby ameliorating the Aβ-induced impairment of AMPA receptor GluR1 expression.The mechanism may be that treadmill exercise increases the expression of VEGF in the brain and activates the VEGF/VEGFR2 pathway.By inhibiting the activation of caspase-3 and the expression of CaN in the brain,VEGF/VEGFR2 pathway improves the expression of AMPA receptor GluR1 and improves the spatial learning and memory ability of APP/PS1 mice. |
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