The copper chelator, D-penicillamine, does not attenuate MPTP induced dopamine depletion in mice

In MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-hydroxydopamine induced dopaminergic neurotoxicity and Parkinson's disease iron accumulates in substantia nigra pars compacta which has been suggested to participate in oxidative stress induced neurodegeneration. Pretreatment with iro...

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Bibliographic Details
Published in:Journal of Neural Transmission 2007-02, Vol.114 (2), p.205-209
Main Authors: Youdim, M B H, Grünblatt, E, Mandel, S
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Animals
Chelating Agents - pharmacology
Chromatography, High Pressure Liquid
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Dopamine - metabolism
Dopamine Agents - toxicity
Iron - metabolism
Male
Mice
Mice, Inbred C57BL
MPTP Poisoning
Nerve Degeneration - prevention & control
Neuroprotective Agents - pharmacology
Penicillamine - pharmacology
Salicylic Acid - pharmacology
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Summary:In MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-hydroxydopamine induced dopaminergic neurotoxicity and Parkinson's disease iron accumulates in substantia nigra pars compacta which has been suggested to participate in oxidative stress induced neurodegeneration. Pretreatment with iron chelators desferal, clioquinol, VK-28 and M30 are neuroprotective in both models. To determine the specificity of chelation neuroprotective activity we have examined the effect of D-penicillamine, a relatively specific copper chelator, in the mice model of MPTP-induced dopamine depletion. Our studies show that D-penicillamine, employed for removal of copper in Wilson disease is relatively weak in preventing dopaminergic neurotoxicity induced by MPTP, as compared to iron chelators previously studied. The results indicate that for prevention of MPTP-induced dopamine depletion and dopamine neurodegeneration, iron rather than copper chelation may be more effective and specific.
ISSN:0300-9564
1435-1463
DOI:10.1007/s00702-006-0499-1