Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1993-10-4
|
| pubmed:abstractText |
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, (MPTP), produces a parkinsonian syndrome both in man and in experimental animals. Its toxicity is mediated by a metabolite, the 1-methyl-4-phenylpyridinium ion (MPP+). When injected into the striatum, MPP+ is accumulated by dopaminergic nerve terminals and retrogradely transported to the substantia nigra pars compacta (SNc) where it causes neuronal degeneration. MPP+ accumulates in mitochondria and blocks complex I of the electron transport chain. A proposed mechanism of neurotoxicity is excitotoxic neuronal degeneration induced by this energy depletion. We examined whether either prior decortication or administration of the N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) could prevent or diminish the selective nigral neuronal degeneration that follows unilateral intrastriatal injection of MPP+. We quantified the extent of neuronal death in the SNc ipsilateral and contralateral to the injections on Nissl-stained sections with unbiased stereological techniques. One week after injection of MPP+, approximately 75% of the SNc neurons were lost on the side of the injection. The loss was a consequence of the reduction in both SNc volume and neuronal density. Both prior decortication or the administration of MK-801 for 2 days nearly completely prevented MPP(+)-induced neuronal loss in the ipsilateral SNc. These results are consistent with an NMDA receptor mediated excitotoxic mechanism for MPP(+)-induced nigral toxicity.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-4-phenyl-1,2,3,6-tetrahydro...,
http://linkedlifedata.com/resource/pubmed/chemical/1-methyl-4-(2'-methylphenyl)-1,2,3,6...,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agents,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0197-4580
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
14
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
295-301
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8103573-1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine,
pubmed-meshheading:8103573-Animals,
pubmed-meshheading:8103573-Cell Count,
pubmed-meshheading:8103573-Cerebral Decortication,
pubmed-meshheading:8103573-Corpus Striatum,
pubmed-meshheading:8103573-Dizocilpine Maleate,
pubmed-meshheading:8103573-Dopamine Agents,
pubmed-meshheading:8103573-Electron Transport,
pubmed-meshheading:8103573-Injections,
pubmed-meshheading:8103573-Injections, Intraperitoneal,
pubmed-meshheading:8103573-MPTP Poisoning,
pubmed-meshheading:8103573-Male,
pubmed-meshheading:8103573-Microscopy,
pubmed-meshheading:8103573-N-Methylaspartate,
pubmed-meshheading:8103573-Nerve Degeneration,
pubmed-meshheading:8103573-Neurons,
pubmed-meshheading:8103573-Rats,
pubmed-meshheading:8103573-Rats, Sprague-Dawley,
pubmed-meshheading:8103573-Substantia Nigra
|
| pubmed:articleTitle |
Blockade of 1-methyl-4-phenylpyridinium ion (MPP+) nigral toxicity in the rat by prior decortication or MK-801 treatment: a stereological estimate of neuronal loss.
|
| pubmed:affiliation |
Massachusetts General Hospital, Boston 02114.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|