NDLI: Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity.

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Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dawson, V. L. Dawson, T. M. Przedborski, S. Shibata, T. Yokoyama, R. Jackson-lewis, V.
Description	Author Affiliation: Przedborski S ( Department of Neurology, Columbia University, New York 10032, USA. sp30@columbia.edu);
Abstract	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic pathway damage similar to that observed in Parkinson disease (PD). To study the role of NO radical in MPTP-induced neurotoxicity, we injected MPTP into mice in which nitric oxide synthase (NOS) was inhibited by 7-nitroindazole (7-NI) in a time- and dose-dependent fashion. 7-NI dramatically protected MPTP-injected mice against indices of severe injury to the nigrostriatal dopaminergic pathway, including reduction in striatal dopamine contents, decreases in numbers of nigral tyrosine hydroxylase-positive neurons, and numerous silver-stained degenerating nigral neurons. The resistance of 7-NI-injected mice to MPTP is not due to alterations in striatal pharmacokinetics or content of 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of MPTP. To study specifically the role of neuronal NOS (nNOS), MPTP was administered to mutant mice lacking the nNOS gene. Mutant mice are significantly more resistant to MPTP-induced neurotoxicity compared with wild-type littermates. These results indicate that neuronally derived NO mediates, in part, MPTP-induced neurotoxicity. The similarity between the MPTP model and PD raises the possibility that NO may play a significant role in the etiology of PD.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dopamine Agents Toxicity MPTP Poisoning Neurons Drug Effects Metabolism Nitric Oxide 3,4-Dihydroxyphenylacetic Acid Animals Cerebellum Pathology Corpus Striatum Dopamine Enzyme Inhibitors Pharmacology Homovanillic Acid Indazoles Isoenzymes Antagonists & Inhibitors Genetics Mice Mice, Inbred C57BL Mice, Mutant Strains Nerve Degeneration Nitric Oxide Synthase Parkinson Disease Etiology Substantia Nigra Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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