Steady Moderate Exercise Confers Resilience Against Neurodegeneration and Neuroinflammation in a Mouse Model of Parkinson’s Disease

Intensive aerobic exercise slows the progression of movement disorders in Parkinson's disease (PD) and is therefore recommended as an important component of treatment for PD patients. Studies in animal models of PD have shown that vigorous exercise has neuroprotective effects, and emerging evidence suggests that it may be a disease-modifying treatment in humans. However, many people with PD may not be able to participate in vigorous exercise because of multiple medical conditions that severely limit their physical activity. In this study, we have shown that chronic MPTP treatment in sedentary mice resulted in loss of dopaminergic neurons in the SNpc, decreased levels of neurotrophins, BDNF and GDNF, and increased levels of inflammatory markers and pro-inflammatory changes in immunocompetent cells. Moderate exercise, initiated both before and after chronic MPTP treatment, significantly attenuated the loss of dopaminergic neurons and increased BDNF and GDNF levels even above those in sedentary control mice. No signs of inflammation were observed in MPTP-treated mice, either when training began before or after MPTP treatment. Training induced beneficial changes in the dopaminergic system, increased levels of neurotrophins and suppression of inflammation were similar for both steady moderate (present data) and intense training (our previously published data). This suggests that there is a kind of saturation when the percentage of rescued dopaminergic neurons reaches the highest possible value, and therefore further increases in exercise intensity do not enhance neuroprotection. In conclusion, our present results compared with the previous data show that increasing exercise intensity beyond the level used in this study does not increase the neuroprotective effect of aerobic training in a mouse model of Parkinson's disease.