Effects of endurance exercise on ventral tegmental area neurons in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid-treated mice

Loss of dopaminergic neurons in the substantia nigra (A9 cells) and ventral tegmental area (VTA) (A10 cells) has been reported in Parkinson's disease with reference to causing motor and non-motor deficits, although clinical and laboratory animal studies on the degeneration of VTA neurons are less emphasized comparative to the degeneration of substantia nigra neurons. In the present study, we examined the VTA dopaminergic neurons in a chronic mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid at a level showing moderate neurodegeneration and studied the impact of endurance exercise on VTA neurons in this model. In comparison to the normal control animals, the chronic mouse model of Parkinson's disease with moderate neurodegeneration demonstrated a significant reduction of VTA neurons (52% loss), when these animals were kept sedentary throughout the study. Morphologically, the VTA dopaminergic neurons in this model displayed a decrease in cell volume and showed irregular or disparaging axonal and dendritic projections. When the chronic Parkinsonian mice were exercised on a motorized rodent treadmill up to 15 m/min, 40 min/day, 5 days/week for 10 and 18 weeks, the total number of VTA dopaminergic neurons were significantly higher than the sedentary Parkinsonian animals. Especially noted with the 18-week exercised Parkinsonian mice, the number of VTA neurons returned to normal range and the cells were densely populated and displayed distinctive axons and dendritic arborization. These results demonstrate that prolonged exercise training is neuroprotective to the dopaminergic neurons in the VTA of the chronic mouse model of Parkinson's disease with moderate neurodegeneration.