The effect of simvastatin in prevention of histological changes of substantia nigra and behavioral abnormalities in an experimental model of Parkinson’s disease in rat

Background and Objective: Parkinson’s disease (PD) is a rather common neurological disorder in elders that is due to degeneration of dopaminergic neurons within mesencephalic substantia nigra pars compacta. With regard to protective and antioxidant effect of simvastatin, this study was conducted to evaluate its neuroprotective effect in an experimental model of PD. Materials and Methods: In this experimental study, male rats (n =40) were divided into 5 groups, i.e. sham-operated, simvastatin20-treated sham-operated, lesioned and simvastatin10 and simvastatin20-treated lesioned groups. The hemi-PD early model was induced by unilateral intrastriatal injection of 5 microliter of saline-ascorbate (left side) containing ?????microgram of ?6-hydroxydopamine (6-OHDA).Treated sham and lesioned groups received simvastatin i.p. at doses of 10 and 20 mg/kg once a day before surgery for two times at an interval of 24 h. Two weeks after surgery, the animals were tested for rotational behavior by apomorphine for an hour and the number of dopaminergic neurons in the substantia nigra pars compacta (SNC) was counted. Results: Two weeks after surgery, apomorphine caused a significant contrala-teral turning (P < 0.0001) in 6-OHDA-lesioned group and a reduction in the number of neurons on the left side of the SNC in the lesioned group was observed in comparison with sham group (P < 0.01). In addition, simvastatin pretreatment at both doses significantly decreased the rotational behavior in lesioned rats (p < 0.05 and p < 0.01, respectively) and also at a higher dose significantly attenuated the reduction in the number of SNC neurons (p < 0.05). On the other hand, pretreatment of sham group with simvastatin had no significant effect on the number of apomophine-induced rotations and neurons of SNC. Conclusion: Intraperitoneal administration of simvastatin exhibits neuroprotective effect against 6-OHDA toxicity in an experimental model of PD, as was shown by a lower rotational behavior and attenuation of neuronal loss.