Objective:To investigate the effect of running excise on dendritic spines in the dentate gyrus（DG）of the hippocampus in middle-aged male APP/PS1 transgenic Alzheimer’s disease（AD）mice using the unbiased stereological methods. Methods:Twelvemonth-old male APP/PS1 transgenic AD mice were randomly assigned to a running group or a positive control group. Meanwhile

agematched male wild-type mice were used as a negative control group（n=15 per group）. The mice of the running group were placed on a treadmill to run for 4 months. The spatial learning and memory abilities were investigated using the Morris water maze test. The density and the total number of the dendritic spines in the DG of the mice in three groups were investigated using the unbiased stereological methods. Results:In the hidden platform task

the escape latency of the running exercise group mice（25.0±2.5）s was significantly shorter than that of the positive control group mice（35.4±2.5）s（P=0.016）. In the probe trial task

the times of platform location crosses

the time spending in the target quadrant（s）and swimming distance percentage in the target quadrant of running group [（3.2 ±1.9）

（21.5 ±7.6） s

（0.31 ±0.12）] were significantly more than positive control group [（1.3 ±0.9）

（14.0 ±8.2） s

（0.23±0.14）]（P=0.01

P=0.029

P=0.019）. The density and the total number of the dendritic spines in the running group [（0.431 9±0.044 8）/μm3

（4.546 6±1.081 4）×108] were significantly increased compared to those of the positive control group[（0.2856 ±0.013 3）/μm3

（2.667 9 ±0.643 5）×108]（P <0.001

P=0.043）. Conclusion:The positive effects of running exercise on the spatial learning and memory abilitiesof APP/PS1 mice might be related to the protective effects ofrunning exercise on the dendritic spines in the DG.