Source:http://linkedlifedata.com/resource/pubmed/id/10192777
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
|
pubmed:dateCreated |
1999-4-21
|
pubmed:abstractText |
Although nontoxic when administered alone, diethyldithiocarbamate (DDC) is known to enhance the dopamine-depleting effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum. The purpose of the present study was twofold: (i) to carefully characterize the effects of DDC on MPTP-induced degeneration of dopaminergic neurons in substantia nigra pars compacta using unbiased, stereological cell counting techniques and (ii) to determine whether or not DDC can convert a nontoxic dose of MPTP into one which is clearly toxic on dopaminergic neurons in the substantia nigra. A single low dose of MPTP (15 mg/kg intraperitoneally (ip)) was used for these studies, which failed to induce any neurochemical or histological effects on the nigrostriatal system of C57BL/6 mice when administered alone. However, when animals were pretreated with DDC (400 mg/kg ip), the same dose of MPTP resulted in a 50% loss of neurons in the substantia nigra pars compacta, as well as a 70% reduction in striatal dopamine (DA). A 31% reduction of DA in the ventral mesencephalon was also seen. This combined regimen of DDC and MPTP was not significantly different from a maximally tolerated "toxic" dose of MPTP alone (15 mg/kg x 4, 1 h apart, ip). As expected, animals receiving DDC alone did not show any dopamine depletion nor nigral neuronal loss. The present study confirms previous work suggesting that DDC enhances MPTP-induced nigral cell loss and shows for the first time that DDC can "unmask" MPTP toxicity. These observations could have implications for theories on the cause of Parkinson's disease.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
0014-4886
|
pubmed:author | |
pubmed:copyrightInfo |
Copyright 1999 Academic Press.
|
pubmed:issnType |
Print
|
pubmed:volume |
156
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
62-70
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:10192777-Animals,
pubmed-meshheading:10192777-Catecholamines,
pubmed-meshheading:10192777-Ditiocarb,
pubmed-meshheading:10192777-Dopamine,
pubmed-meshheading:10192777-Dopamine Agents,
pubmed-meshheading:10192777-Drug Synergism,
pubmed-meshheading:10192777-Immunohistochemistry,
pubmed-meshheading:10192777-MPTP Poisoning,
pubmed-meshheading:10192777-Male,
pubmed-meshheading:10192777-Mesencephalon,
pubmed-meshheading:10192777-Mice,
pubmed-meshheading:10192777-Mice, Inbred C57BL,
pubmed-meshheading:10192777-Neostriatum,
pubmed-meshheading:10192777-Substantia Nigra,
pubmed-meshheading:10192777-Tyrosine 3-Monooxygenase
|
pubmed:year |
1999
|
pubmed:articleTitle |
Diethyldithiocarbamate causes nigral cell loss and dopamine depletion with nontoxic doses of MPTP.
|
pubmed:affiliation |
Department of Neuroscience, Doktorsringen 17 Karolinska Institutet, S-17177, Stockholm, Sweden.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|