Source:http://linkedlifedata.com/resource/pubmed/id/19007862
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2009-1-19
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| pubmed:abstractText |
The neurotoxin 6-hydroxydopamine has been widely used to model aspects of Parkinson's disease in rodents, but the mechanisms underlying toxin-induced dopaminergic degeneration and functional impairment have not been fully elucidated. The main aim of the present study was to assess a possible role for calpains in neurochemical and behavioral deficits following unilateral infusion of intrastriatal 6-hydroxydopamine in adult rats. Toxin administration produced a profound dopaminergic denervation, as indicated by a 90-95% reduction in dopamine transporter radiolabeling measured in the caudate-putamen at 2 weeks post-lesion. Treatment with 6-hydroxydopamine also resulted in calpain activation in both caudate-putamen and substantia nigra, as measured by the appearance of calpain-specific spectrin breakdown products. Calpain activation peaked at 24 h after 6-hydroxydopamine infusion and remained elevated at later time points. In contrast, caspase-3-mediated spectrin cleavage subsided within 48 h in both brain areas. In a subsequent experiment, calpain inhibition was achieved by intrastriatal infusion of an adenovirus expressing the endogenous calpain inhibitor, calpastatin. Calpastatin delivery abolished the lesion-induced calpain-mediated spectrin cleavage and alleviated forelimb asymmetries resulting from unilateral intrastriatal 6-hydroxydopamine. Unexpectedly, dopamine transporter and tyrosine hydroxylase labeling revealed significant neuroprotection, not in the nigrostriatal pathway but rather in the ventral tegmental area. These findings support a role for calpain activation in 6-hydroxydopamine-induced degeneration of dopaminergic neurons. However, after near-total dopaminergic depletion, the primary benefit of calpain inhibition may not occur within the nigrostriatal dopaminergic pathway itself.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calpain,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Plasma Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/RTI 55,
http://linkedlifedata.com/resource/pubmed/chemical/Spectrin,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/calpastatin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0306-4522
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
23
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| pubmed:volume |
158
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
558-69
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| pubmed:meshHeading |
pubmed-meshheading:19007862-Adrenergic Agents,
pubmed-meshheading:19007862-Animals,
pubmed-meshheading:19007862-Autoradiography,
pubmed-meshheading:19007862-Calcium-Binding Proteins,
pubmed-meshheading:19007862-Calpain,
pubmed-meshheading:19007862-Caspase 3,
pubmed-meshheading:19007862-Cocaine,
pubmed-meshheading:19007862-Corpus Striatum,
pubmed-meshheading:19007862-Dopamine,
pubmed-meshheading:19007862-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:19007862-Functional Laterality,
pubmed-meshheading:19007862-Green Fluorescent Proteins,
pubmed-meshheading:19007862-Male,
pubmed-meshheading:19007862-Motor Activity,
pubmed-meshheading:19007862-Oxidopamine,
pubmed-meshheading:19007862-Psychomotor Performance,
pubmed-meshheading:19007862-Rats,
pubmed-meshheading:19007862-Rats, Sprague-Dawley,
pubmed-meshheading:19007862-Spectrin,
pubmed-meshheading:19007862-Time Factors,
pubmed-meshheading:19007862-Tyrosine 3-Monooxygenase
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| pubmed:year |
2009
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| pubmed:articleTitle |
Effects of calpain inhibition on dopaminergic markers and motor function following intrastriatal 6-hydroxydopamine administration in rats.
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| pubmed:affiliation |
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler Room 1325, Montreal, Quebec, Canada H3G 1Y6.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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