Neuroprotective Effects of Pramipexole in Parkinson s Disease Induced by Rotenone in Mice

Background: Pramipexole (PPX), an agonist for Dopamine (DA), has been used to treat both early and advanced Parkinson s Disease (PD).Objectives: This study was done to evaluate the neuroprotective effect of PPX in a DA neuron degeneration model of PD induced by rotenone.Methods: Thirty six male mice were used and divided into three equal groups. The first group, the control group, received only the vehicle (sunflower oil) for a period of 7 weeks (49 days). The second group received rotenone (2mg/kg; IP) dissolved in sunflower oil daily for 49 days. The third group received a combined treatment of rotenone (2mg/kg, IP) and PPX (1mg/kg, IP) daily for 49 days. Behavioral tests were performed a day prior to drug administration and then once weekly along the duration of drugs or vehicle administration. At the end of the 49 days all animals were sacrificed and their midbrains were subjected to immunohistochemical analysis for dopaminergic neurons staining for Anti-Tyrosine Hydroxylase (TH) antibodies. Midbrain tissues were also isolated for biochemical measurements.Results: Behavioral tests revealed that PPX counteracted the rotenone effect in mice locomotor activity and catalepsy. Immunohistochemistry results showed that PPX inhibited the rotenone-induced loss of TH-immunopositive neurons in the substantia nigra pars compacta. Biochemical measurements demonstrated that PPX treatment significantly reversed the rotenone-induced decrease in midbrain DA level. Interestingly, PPX ameliorate the rotenone-induced increase in the malondialdehyde and nitric oxide levels as well as the decrease in total antioxidant capacity.Conclusion: The results indicate the beneficial effect of PPX against the dopaminergic neurodegeneration induced by chronic IP administration of rotenone. This neuroprotective effect seems to be mediated by inhibition of rotenone induced oxidative stress and nitric oxide overproduction and through maintenance of the cellular antioxidant status.