Delayed Exercise-Induced Functional and Neurochemical Partial Restoration Following MPTP

Abstract

In two experiments, MPTP was administered to C57/BL6 mice according to a single-dose weekly regime (MPTP: 1 × 30 mg/kg on the fifth day of the week, Friday, over 4 weeks) with vehicle group (Vehicle: 1 × 5 ml/kg) treated concurrently. Exercise schedules (delayed) were introduced either at the beginning of the week after the second MPTP injection (MPTP + Exercise(2) group), or at the beginning of the week after the fourth MPTP injection (MPTP + Exercise(4) group). Wheel-running was provided on the first 4 days of each week (Monday-Thursday) more than 30-min periods. In Experiment I, wheel-running exercise was introduced either after 2 or 4 weeks after MPTP/Vehicle. MPTP and Vehicle groups not provided access to the running wheels were placed in single cages within the wheel-running room over 30-min concomitantly with the wheel-running groups. In Experiment II, wheel-running exercise was introduced 2 weeks after MPTP/Vehicle but a no-exercise control group with non-revolving wheel included (MPTP-Wheel). In both experiments, spontaneous motor activity tests during 60-min intervals were performed at the end (Fridays) of weeks 1, 2, 3, 4, 6, 8, and 10, where the week on which the first injection of MPTP was the first week; in the case of weeks 1-4, this was immediately before MPTP/Vehicle injections. It was observed that the introduction of the exercise schedule after the second MPTP injection, but not after the fourth injection, restored motor activity that had been markedly elevated by the end of the tenth week. Subthreshold administration of L-dopa tests was performed after the spontaneous motor activity tests 6, 8 and 10; these indicated significant effects of exercise, MPTP + Exercise(2) group, on Tests 6 and 8, but not Test 10. The physical exercise schedule in that group also showed markedly attenuated loss of dopamine (DA). Restoration of MPTP-induced motor activity deficits and DA loss was a function of the point at which exercise was introduced, in the present case after two administrations of the neurotoxin. In Experiment II, physical exercise markedly attenuated the hypokinesic effect of MPTP in the exercise condition, MPTP-exercise, but not in the non-exercise conditions, MPTP-Cage and MPTP-Wheel, for both spontaneous motor activity and L-dopa-induced activity. MPTP-induced loss of DA was also attenuated by exercise.