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Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents
 
Creator Borah, Anupom
Mohanakumar , K P
 
Subject Cell Biology & Physiology
 
Description 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.
 
Publisher Blackwell Publishing
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/229/1/JOURNAL_OF_PINEAL_RESEARCH%2C47(4)%2C293%2D300%2C2009[13].pdf
Borah, Anupom and Mohanakumar , K P (2009) Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents. Journal Of Pineal Research, 47 (4). pp. 293-300.
 
Relation http://dx.doi.org/10.1111/j.1600-079X.2009.00713.x
http://www.eprints.iicb.res.in/229/