TREADMILL EXERCISE TRAINING INDUCES ANGIOGENESIS and IMPROVES ENDURANCE and NEURONAL INDICATORS IN CHRONIC MOUSE MODEL OF PARKINSON'S DISEASE.

Abstract

Purpose/Hypothesis: The goal of this study was to determine whether a 4-week treadmill running protocol could induce angiogenesis and improve endurance and neuronal indicators in a chronic MPTP/probenecid mouse model of Parkinson's disease. Number of Subjects: Twenty-three C57BL/6 mice were randomly assigned in 4 groups: sedentary control, exercise-trained control, sedentary PD, and exercise-trained PD. Materials/ Methods: The PD was induced by 10 chronic injections of 25 mg/kg MPTP and 250 mg/kg probenecid, which exhibited many symptoms of human PD. Exercised groups of mice were trained to run 40 min, 5 days/week for 4 weeks at an average speed of 18 m/min on a treadmill. Citrate synthase activity, cardiovascular parameters, dopamine level in sub-stantia nigra, tyrosine hydroxylase contents and blood vessels density in the striatum were analyzed and compared between the animal groups. Results: Compared to the respective sedentary groups, the soleus muscle citrate synthase activity increased by 21% in the exercise-trained PD group and 18% in the exercise-trained control group (p < 0.05). Citrate synthase activity in the gastrocnemius produced similar results. Resting heart rates declined significantly in both exercise-trained groups. PD showed a decrease in the resting heart rate by about 10%. Substantia nigra tyrosine hydroxylase content and striatal dopamine levels were increased nearly 30% in the exercise-trained PD over the sedentary PD mice, whereas these levels were indifferent between sedentary and exercise-trained controls. Exercise also resulted in a significant increase in blood vessel density in the striatum of trained PD animals compared to the sedentary group (p < 0.003). Conclusions: In summary, our study demonstrated that improvement in endurance and neuronal parameters as well as angiogenesis could be achieved in PD mice with a 4-week exercise training protocol. Clinical Relevance: According to our results, aerobic exercise could be beneficial for limited functional recovery in subjects with debilitating neurodegener-ative disorders, including Parkinson's disease