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Melatonin attenuates MPP + ‐induced neurodegeneration and glutathione impairment in the nigrostriatal dopaminergic pathway
Author(s) -
Chen Shur Tzu,
Chuang Jih Ing,
Hong Mei Huei,
Li Eric IChian
Publication year - 2002
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2002.01871.x
Subject(s) - substantia nigra , melatonin , glutathione , neuroprotection , neurodegeneration , oxidative stress , dopaminergic , endocrinology , chemistry , nigrostriatal pathway , medicine , buthionine sulfoximine , striatum , parkinson's disease , pharmacology , dopamine , biology , biochemistry , disease , enzyme
In this study we selected a rat model of Parkinson's disease (PD) by using intrastriatal infusion of the 1‐methyl‐4‐phenyl‐pyridinium ion (MPP + ) to investigate the neuroprotective action of melatonin and its inhibitory activity on MPP + ‐impaired glutathione (GSH) system in the nigrostriatal system. Results show that MPP + caused not only a severe neuronal injury in the striatum and in the ipsilateral substantia nigra (SN), but it also induced a significant decrease in GSH levels and an increase in the GSSG/GSH ratio 3 days after intrastriatal MPP + infusion. Intraperitoneal co‐administration of melatonin (10 mg/kg, five times) significantly attenuated MPP + ‐induced nigrostriatal neurotoxicity and GSH impairment. Depletion of cytosolic GSH by L‐buthionine sulfoximine (BSO) did not cause neuronal damage by itself. It, however, when co‐administrated with MPP + , potentiated the GSH reduction in the striatum, without aggravating nigrostriatal neurodegeneration induced by MPP + . Moreover, the MPP + ‐caused neuronal damage was positively correlated with a rising ratio of GSSG/GSH, but not with a drop of GSH. These results suggest that the MPP + ‐triggered oxidative stress may play a more important role than the loss of the antioxidant GSH in determining neuronal injury. Interestingly, the neuronal damage and oxidative stress elicited by co‐treatment of BSO with MPP + were effectively reduced by melatonin. Our results hence provide direct evidence showing that melatonin attenuates MPP + ‐induced nigrostriatal dopaminergic injury by its ability to impede the increase of GSSG/GSH ratio; therefore melatonin may have therapeutic implications in PD.