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Melatonin inhibits 6‐hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents
Author(s) -
Borah Anupom,
Mohanakumar Kochupurackal P.
Publication year - 2009
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 - 10.1111/j.1600-079x.2009.00713.x
Subject(s) - melatonin , mptp , hydroxydopamine , parkinsonism , dopaminergic , dopamine , neurotoxin , neuroprotection , medicine , endocrinology , oxidopamine , medial forebrain bundle , striatum , parkinson's disease , chemistry , pharmacology , biology , substantia nigra , disease
We tested the hypothesis that melatonin regulates formation of 6‐hydroxydopamine (6‐OHDA) in the brain and thereby protects animals from dopaminergic neurotoxicity and the development of parkinsonism in animals. Employing a ferrous‐ascorbate‐dopamine (FAD) hydroxyl radical ( • OH) generating system, in the present study we demonstrate a dose‐dependent attenuation of 6‐OHDA generation by melatonin in vitro. Intra‐median forebrain bundle infusion of FAD caused significant depletion of striatal dopamine (DA), which was blocked by melatonin. Per‐oral administration of l ‐3,4‐dihydroxyphenylalanine (l ‐DOPA) for 7 days caused a dose‐dependent increase in the formation of 6‐OHDA in the mouse striatum, which was increased synergistically by the systemic administration of the parkinsonian neurotoxin, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) on the 7th day of l ‐DOPA treatment. Melatonin treatment significantly attenuated both the l ‐DOPA and MPTP‐induced increases in the levels of striatal 6‐OHDA, and protected against striatal DA depletion caused by the neurotoxin. These observations suggest a novel mode of melatonin‐induced dopaminergic neuroprotection in two models of Parkinson’s disease, and suggest the possible therapeutic use of this well‐known antioxidant indoleamine neurohormone in parkinsonism.