Exercise Evokes Retained Motor Performance without Neuroprotection in a Mouse Model of Parkinson’s Disease

Exercise has been extensively studied in Parkinson’s Disease, with a particular focus on the potential for neuroprotection that has been demonstrated in animal models. While this preclinical work has provided insight into the underlying molecular mechanisms, it has not addressed the neurophysiological changes during exercise. Here, first, we tested for neuroprotective effects of adaptive wheel exercise in the 6-hydroxydopamine mouse model of Parkinson’s disease. Finding none, we probed the neurophysiology of exercise as a state of high motor function amidst an unameliorated Parkinsonian lesion. Exercise was associated with characteristic, excitatory changes in the dopamine-depleted substantia nigra, which could be suppressed along with exercise itself by dopamine receptor blockade. Going forward, the functional state evoked by exercise merits further study, as it may represent an optimal target for neuromodulation, even if the underlying pathology cannot be averted.