Effects Of Exercise Intervention On Axonal Transport Dependent On Mitochondria Of Kinesin In AD Model

Objective:To observe the effect of 8 weeks aerobic exercise on anterograde axonal transport of mitochondrial kinesin in the cortex and hippocampus of AD mouse, and to provide a biological basis for the exercise improving learning and memory ability in AD mice.Methods:40 SPF 4 months APP/PSl transgenic mice and C57BL/6J mice were randomly divided into sedentary(AS、CS) and exercise groups (AE、CE) respectively. The exercised groups were subjected to a 8w treadmill exercise at the speed of 15m/min on an 0% slope for 10min/d then 18m/min for 50min/d (for a total of 60min),5d/week. The mitochondrial morphology and number in the brain tissue was detected by transmission electron microscope; The protein levels of KHC、KLC1、KLC2 were measured using western blot.Results:(1)In 6-month-old APP/PSl mice, the transmission electron showed the neuropil structures in the cortex and hippocampus were loose, the typical synaptic structures were less than the control groups. Mitochondria swollen and membranes ruptured were observed. The number of abnormal mitochondria were increased. After 8 weeks aerobic exercise, the typical synaptic structure were found, the number of orderly arranged synaptic vesicle were increased, and the number of abnormal mitochondria were decreased. (2) The expression of KHC, KLC1, KLC2 in the frontal cortex and temporal lobe of 6 month-old APP/PS1 mice were decreased compared with the normal control group. After 8 weeks aerobic exercise the expression of KHC, KLC1, KLC2 in cortex were significantly increased. But there was no significant difference in KLC2 upregulation of temporal lobe. (3) Compared with those of the normal control group, the expression of KHC, KLC1, KLC2 in hippocampus of 6-month-old APP/PS1 mice were decreased. Aerobic exercise significantly increased the expression of KHC, KLC1, KLC2 in CA3 region. (4) In the 6-month-old C57BL/6J control groups the transmission electron showed the structure of mitochondria and synapse clear and complete, the number of mitochondria was large and well-distributed. In aerobic exercise control group the number of abnormal mitochondria trends to reduced, while the expression of KLC2 in hippocampus was significantly increased and the KHC, KLC1 in CA1 region.Conclusion:8 weeks aerobic exercise can mediate defective transport of axonal mitochondria by upregulation the levels of Kinesin heavy chain and light chain in APP/PS1 transgenic mice, thereby increasing the distribution of mitochondria in synapse and improving the synaptic structure and function, which maybe is one of the underlying molecular mechanism of exercise-induced beneficially affecting brain function.