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| Research article summary (published 6 May 2009): |
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Striatal neuroinflammation promotes Parkinsonism in rats.
Full Abstract
BACKGROUND: Sporadic Parkinson's disease (PD) is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors contribute to dopaminergic neuronal death in PD. FINDINGS: In this study, we analyzed the relationship among inducible nitric oxide synthase (iNOS)-derived NO, mitochondrial dysfunction and dopaminergic neurodegeneration to examine the possibility that microglial neuroinflammation may induce dopaminergic neuronal loss in the substantia nigra. Unilateral injection of lipopolysaccharide (LPS) into the striatum of rat was followed by immunocytochemical, histological, neurochemical and biochemical analyses. In addition, behavioral assessments including cylinder test and amphetamine-induced rotational behavior test were employed to validate ipsilateral damage to the dopamine nigrostriatal pathway. LPS injection caused progressive degeneration of the dopamine nigrostriatal system, which was accompanied by motor impairments including asymmetric usage of forelimbs and amphetamine-induced turning behavior in animals. Interestingly, some of the remaining nigral dopaminergic neurons had intracytoplasmic accumulation of alpha-synuclein and ubiquitin. Furthermore, defect in the mitochondrial respiratory chain, and extensive S-nitrosylation/nitration of mitochondrial complex I were detected prior to the dopaminergic neuronal loss. The mitochondrial injury was prevented by treatment with L-N(6)-(l-iminoethyl)-lysine, an iNOS inhibitor, suggesting that iNOS-derived NO is associated with the mitochondrial impairment. CONCLUSIONS: These results implicate neuroinflammation-induced S-nitrosylation/nitration of mitochondrial complex I in mitochondrial malfunction and subsequent degeneration of the nigral dopamine neurons.
Author information
Author/s: Choi, Dong-Young (DY); Liu, Mei (M); Hunter, Randy L (RL); Cass, Wayne A (WA); Pandya, Jignesh D (JD); Sullivan, Patrick G (PG); Shin, Eun-Joo (EJ); Kim, Hyoung-Chun (HC); Gash, Don M (DM); Bing, Guoying (G);
Affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, United States of America.
Grants: NS044157 (Agency:NINDS NIH HHS) ; NS39345 (Agency:NINDS NIH HHS)
Journal and publication information
Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Journal: PloS one (PLoS One), published in United States. (Language: eng)
Reference: 2009-; vol 4 (issue 5) : pp e5482
Dates: Created 2009/05/08; Completed 2009/06/17;
PMID: 19424495, status: MEDLINE (last retrieval date: 6/17/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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