MELATONIN PROTECTS NIGRAL DOPAMINERGIC-NEURONS FROM 1-METHYL-4-PHENYLPYRIDINIUM (MPP+) NEUROTOXICITY IN RATS

In the present study, the in vivo neuroprotective effects of melatonin , as an antioxidant, were assessed in Sprague-Dawley rats with a unila teral lesion of substantia nigra (SN) caused by a stereotaxic injectio n of neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). When expressed as a percentage ratio of lesioned to intact side, increased lipid peroxi dation product (malondialdehyde, MDA, 117% of control) and decreased t yrosine hydroxylase (TH) enzyme activity (60% of control) in SN were o bserved 4 h after MPP- lesion. In contrast, however, melatonin treatme nt prevented MPP+ neurotoxicity by the almost complete recovery of MDA (99% of control) and TH levels (96% of control), indicating the poten t antioxidative effects of melatonin. In addition, further reduction o f TH enzyme activity (52% of control) was seen 1 week after MPP+ infus ion. Continuous (twice a day for 5 days), not acute (4 h) treatment wi th melatonin produced the partial, but not statistically significant, recovery of TH enzyme activity (71% of control), when sacrificed 1 wee k after MPP+ lesion. Taken together, the present results support the h ypothesis that melatonin may provide the useful therapeutic strategies for the treatment of oxidative stress-induced neurodegenerative disea se such as Parkinson's disease (PD). (C) 1998 Published by Elsevier Sc ience Ireland Ltd.