Document Detail

7-nitroindazole protects striatal dopaminergic neurons against MPP+-induced degeneration: an in vivo microdialysis study.
MedLine Citation:
PMID:  17261789     Owner:  NLM     Status:  MEDLINE    
The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP(+)) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP(+)-lesioned, and (c) 7-NI pretreated MPP(+)-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP(+) was infused into the striatum for 10 min in the other two groups. The infusion of the MPP(+) produced a neurotoxic damage of the SNc DA neurons and increased striatal DA levels. On day 2, 1 mM MPP(+) was reperfused for 10 min into the striata of each rat group and DA levels were measured as an index of neuronal cell integrity. The limited rise of DA following MPP(+) reperfusion in the MPP(+)-lesioned rats was due to toxin-induced neuronal loss and was reversed by pretreatment with 7-NI (50 mg/kg, intraperitoneally) on day 1, indicating a neuroprotective effect by inhibiting NO formation. These results indicate that neuronally derived NO partially mediates MPP(+)-induced neurotoxicity. The similarity between the MPP(+) model and PD suggests that NO may play a significant role in its etiology.
Vincenzo Di Matteo; Arcangelo Benigno; Massimo Pierucci; Davide Antonio Giuliano; Giuseppe Crescimanno; Ennio Esposito; Giuseppe Di Giovanni
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1089     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2007-01-30     Completed Date:  2007-03-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  462-71     Citation Subset:  IM    
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (CH), Italy.
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MeSH Terms
1-Methyl-4-phenylpyridinium / antagonists & inhibitors,  toxicity
Disease Models, Animal
Dopamine / metabolism*
Enzyme Inhibitors / pharmacology
Indazoles / pharmacology
Neurons / drug effects,  enzymology*,  pathology
Neuroprotective Agents / pharmacology
Nitric Oxide Synthase Type I / antagonists & inhibitors,  physiology*
Parkinson Disease / enzymology,  etiology*,  pathology
Rats, Sprague-Dawley
Substantia Nigra / drug effects,  enzymology*,  pathology
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Indazoles; 0/Neuroprotective Agents; 2942-42-9/7-nitroindazole; 48134-75-4/1-Methyl-4-phenylpyridinium; EC Oxide Synthase Type I

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