Source:http://linkedlifedata.com/resource/pubmed/id/15384065
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2004-10-6
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pubmed:abstractText |
When infused in rats, rotenone, a mitochondrial complex I inhibitor, induces alterations that resemble the histological changes of Parkinson's disease, particularly degeneration of the nigrostriatal dopaminergic system. However, the specificity of rotenone effects has been challenged recently. We have re-examined the alterations caused by rotenone in the substantia nigra and the striatum of rats after infusion of rotenone (2 mg/kg per day s.c.) for 21 days. Three patterns of striatal tyrosine-hydroxylase immunoreactivity (TH-IR) were observed: 46% of animals showed no reduction, and 46% of animals showed diffuse reduction in TH-IR, whereas one animal presented a focal loss of TH-IR in the striatum. Confocal microscopy analysis showed that the vesicular monoamine transporter (VMAT2) was decreased in parallel with TH-IR, strongly suggesting a loss of striatal DA nerve terminals in animals with diffuse or central TH-IR loss. However, no significant loss of TH-IR neurons was observed in the substantia nigra. Analysis of NeuN and DARPP-32 immunoreactivity, and Nissl staining, in the striatum showed no striatal neuronal loss in animals with either preserved TH-IR or diffuse TH-IR reduction. However, in the animal with focal TH-IR loss, severe neuronal loss was evident in the center and the periphery of the striatum, together with microglial activation detected by OX-6 and OX-42 staining. Thus, in most cases, chronic subcutaneous infusion of low doses of rotenone does not induce significant striatal neuronal loss, despite TH-IR and VMAT-IR reduction in a subset of animals, supporting the use of rotenone as a model of Parkinson's disease under carefully controlled experimental conditions.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9967
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pubmed:author | |
pubmed:copyrightInfo |
2004 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
478
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
418-26
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading | |
pubmed:year |
2004
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pubmed:articleTitle |
Variable effects of chronic subcutaneous administration of rotenone on striatal histology.
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pubmed:affiliation |
Departments of Neurology and Neurobiology, The David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-1769, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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