Melatonin is protective against MPTP-induced striatal and hippocampal lesions

The in vivo effect of melatonin on MPTP-induced neurotoxicity in mouse brain was studied. Melatonin (10 mg/kg) or saline was administered intraperitoneally (ip) to mice 30 min prior to a sc injection of MPTP (20 mg/kg). After MPTP treatment, the animals received melatonin or saline injections every hour for three hours. Mice were killed 4 hours after the MPTP injection. Regionally-specific increases in lipid peroxidation were observed in corpus striatum and hippocampus (71% and 58%, respectively), but not in cerebral cortex, cerebellum or midbrain. Treatment with melatonin completely reversed the rises in lipid peroxidation products. MPTP-treated mice showed a significant decrease in the striatal tyrosine hydroxylase immunoreactive nerve terminals, an effect that was also prevented by melatonin. These data show that melatonin is neuroprotective in this MPTP model of Parkinson's disease and suggest that melatonin, an endogenous antioxidant and nontoxic compound, may have potential beneficial effects for this neurodegenerative disorder.