Effects Of 8 Weeks Treadmill On Space Learning Memory In APP Mice

Objective:To investigate the effects of 8 weeks on space learning memory and to underly the possible molecular mechanisms for regular exercise beneficially affects brain function in APP transgenic mice.Methods:Thirty-two male APP mice were randomly assigned to either a sedentary control (C) or an exercise training group(8 weeks treadmill, E). At the same time sixteen C57 mice were designed as negative control group. All experimental subjects were divided into three groups:normal group (N), APP group (C), exercise+APP group (E). Exercise protocol:the training animals ran 10 min/day at 15m/min on an 0% slope then 50min/day at 18m/min for 5 times every week. Time and speed were continued for 8 wk. Animals used for water maze tasks were not tested for molecular biological analyse, also animals used for molecular biological analyse would not be used for the behavioral testing. The animals used for molecular biological analyse were killed 24 h after the last training session.After the last training session, testing method are as follows:1) Morris water maze was used to test the space learning and memory ability of the mice from behaviouristics;2) Western blot was used to detect AMPA receptors GluRl-S831 and GluRl-S845 phosphorylation degree of the mice in the hippocampus and cortex;3) Enzymoimmunoassay method was used to detect the cAMP concentration changes in the hippocampus and cortex of miceResults:1) Morris water maze test results:the normal group and APP+ exercise group's average search platform time and the average search platform route was significantly lower compared with APP group (P<0.01). 2) APP+exercise group's AMPA receptors GluRl-S831 and GluRl-S845 phosphorylation degree in the hippocampus was significantly increased compared with the APP group (P＜0.01), and the difference from normal group was not obvious, APP+exercise group's AMPA receptors GluR1-S831 phosphorylation in cotex was slightly higher than the APP group,but APP+exercise group's AMPA receptors GluRl-S845 phosphorylation wad slightly lower than APP groups, but compared with normal was significantly higher.3)After eight weeks treadmill exercise, APP+exercise group cAMP concentration in the hippocampus was significantly higher than APP group. Comparing to normal group, it was not statistically significant, APP group's cAMP concentration in the cortex were significantly increased than APP+exercise group and the normal group (P< 0.01).Conclusion:8 weeks treadmill can increase the space learning and memory ability of APP mice, which maybe mainly through improving the hippocampus AMPA receptors phosphorylation degree and the concentration of intracellular second messenger-cAMP. But its effect on the cortex was different from the hippocampus, the specific mechanism needs further research.