Physiological mechanisms of improvement with exercise in the mouse model of chronic Parkinson's disease.

摘要

Parkinson's disease (PD) is a progressive disorder of the nervous system that results from a shortage of the neurotransmitter, dopamine. It is generally accepted that exercise improves the well being of people with PD, but the physiological mechanisms explaining the improvement are unknown. The goal of this study was to elucidate the mechanisms of exercise, focusing on the areas of the brain affected by PD (substantia nigra and striatum), along with the non-neuronal effects of treadmill exercise. We used a model of chronic parkinsonianism using MPTP and probenecid injections. The mice were randomly assigned into 4 groups: sedentary control, exercised control, sedentary parkinsonian, and exercised parkinsonian. Exercised mice were trained to run on a treadmill 40 min/day, 5 days/week for 4 weeks at an average speed of 18 m/min. At the completion of the training period, resting heart rates declined significantly in both exercise-trained groups, and the increase in ECG R wave amplitude noted with parkinsonism was blocked with exercise training. Indirect calorimetry illustrated that the volume of oxygen uptake (VO2), carbon dioxide production (VCO2,), and heat production (kcals) were significantly lower in the exercised parkinsonian animals compared to the sedentary parkinsonian mice. Compared to the sedentary groups, soleus muscle citrate synthase activity increased by 21% in the exercised parkinsonian group and 18% in the exercise-trained control group (p0.05). Citrate synthase activity in the gastronemius muscle produced similar results. The endothelial cell marker (VEGF receptor) was upregulated in the striatum of the brain; however, immunohistochemistry revealed that the increase was not in the endothelial cells, as assumed, but in the neurons. Another angiogenesis marker, vonWilebrand Factor, demonstrated an increase in blood vessels with exercise in the PD model. The level of glial derived neurotrophic factor in the substantia nigra of the brains showed no significant change with exercise in the PD animals. The results of our study demonstrated that improvement in endurance and cardiorespiratory parameters as well as increased angiogenesis could be achieved in parkinsonian mice with a 4-week exercise protocol. However, exercise did not significantly improve the level of neurotrophic factors in the brain of Parkinsonian mice.