Abstract
Neuronal oxidative stress and mitochondrial dysfunction have been implicated in Parkinson's disease (PD). We have recently correlated striatal dopaminergic (DA) neurodegeneration with mitochondrial deficit in a chronic mouse model of PD (MPD) induced by 10 injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine and probenecid over 5 weeks. Melatonin is a natural antioxidant and free radical scavenger, which has been shown to reduce cellular oxidative stress, protect mitochondria, and slow aging. In this study, we examined the effect of long‐term melatonin treatment (5 mg/kg/day, i.p., 5 days/week for 18 weeks) on mitochondrial and DA neuronal functions in the striatum of the chronic MPD. Melatonin alone did not alter the normal neuronal, mitochondrial and motor functions as seen in the saline‐treated control mice. The chronic MPD exhibited marked loss of DA, reduction of mitochondrial respiration and ATP level in the striatum, and impaired motor performance on the challenging beam. Interestingly, melatonin treatment for 18 weeks significantly reduced DA loss and motor impairment and prevented mitochondrial deficit as detected in the chronic MPD. This study demonstrates that long‐term melatonin is not only mitochondria‐protective but also neuroprotective in the chronic MPD supporting the hypothesis that melatonin may slow the progression of PD neurodegeneration. Supported by NINDS R01 NS47920.
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