and Aim: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is one of neurotrophines' family which improves the dopaminergic cells survival and activity. The purpose of the current study was to investigate the protective effects of 12 weeks of voluntary exercise on MANF level in the brainstem of parkinsonian rats against the destruction of substansia nigra's dopaminergic cells using 6-hydroxydopamine. Materials and Methods: In this experimental study, twenty-five male rats were divided

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... nto three groups: Base (healthy control, n=9), control-Parkinson (n=9), and voluntary exercise-parkinsonian (n=7). The voluntary exercise control group/ healthy group (n=9) were housed in individual cages geared with running wheels and had activity for 12 weeks. To induce parkinson in the second group (n=9), 250 microgram in 5 microliter 6-OHDA (dissolved in saline) was administered intracerebroventricularly (ICV) using a stereotaxic apparatus.The third healthy exercise group only had voluntary exercise for the same period. Finally, MANF levels in the brainstems were measured by means of ELISA. The obtained data was analyzed using one-way variance analysis (ANOVA) and Tukey post hoc. Results: Mean running distance of the subjects was 5384±764/16 meter per day. In this study MANF levels between exercise group and Parkinson control had significant differences (P=.001). In other words, decrease in MANF levels was prevented in the exercise group (P=.001). MANF levels in the exercise group remained almost at the same level as the Base group (healthy control), P=0.615) Conclusion: voluntary exercises cause the amplification of MANF against oxidative damage induced by 6-OHDA toxicity and have a protective role against parkinson.