Exercise: is it a neuroprotective and if so, how does it work?

There is clinical evidence that the symptoms of Parkinson's disease can be ameliorated by physical exercise, and we have been using animal models to explore the hypothesis that such exercise can also be neuroprotective. To do so we have focused on models of the dopamine deficiency associated with motor symptoms of parkinsonism, including mice treated systemically with MPTP and rats treated with 6-hydroxydopamine. Our focus on exercise derives in part from the extensive literature on the ability of exercise to increase mitochondrial respiration and antioxidant defenses, and to stimulate neuroplasticity. Beginning with constraint therapy and then employing wheel running and environmental enrichment, we have shown that increased limb use can reduce the behavioral effects of dopamine-directed neurotoxins and reduce the loss of dopamine neurons that would otherwise occur. While the mechanism of these effects is not yet known, we suspect a central role for neurotrophic factors whose expression can be stimulated by exercise and which can act on dopamine neurons to reduce their vulnerability to toxins. We believe these data, together with observations from several other laboratories, suggest that exercise, as well as neurotrophic factors, is likely to be an effective neuroprotective strategy in the treatment of Parkinson's disease.