Linked Life Data

15890010

Source:http://linkedlifedata.com/resource/pubmed/id/15890010

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2005-5-13
pubmed:abstractText
The herbicide paraquat (PQ) has been implicated as a potential risk factor for the development of Parkinson's disease. In this study, PQ (0.5-1 microM) was shown to be selectively toxic to dopaminergic (DA) neurons through the activation of microglial NADPH oxidase and the generation of superoxide. Neuron-glia cultures exposed to PQ exhibited a decrease in DA uptake and a decline in the number of tyrosine hydroxylase-immunoreactive cells. The selectivity of PQ for DA neurons was confirmed when PQ failed to alter gamma-aminobutyric acid uptake in neuron-glia cultures. Microglia-depleted cultures exposed to 1 microM PQ failed to demonstrate a reduction in DA uptake, identifying microglia as the critical cell type mediating PQ neurotoxicity. Neuron-glia cultures treated with PQ failed to generate tumor necrosis factor-alpha and nitric oxide. However, microglia-enriched cultures exposed to PQ produced extracellular superoxide, supporting the notion that microglia are a source of PQ-derived oxidative stress. Neuron-glia cultures from NADPH oxidase-deficient (PHOX-/-) mice, which lack the functional catalytic subunit of NADPH oxidase and are unable to produce the respiratory burst, failed to show neurotoxicity in response to PQ, in contrast to PHOX+/+ mice. Here we report a novel mechanism of PQinduced oxidative stress, where at lower doses, the indirect insult generated from microglial NADPH oxidase is the essential factor mediating DA neurotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1523-0864
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
654-61
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:articleTitle
The role of microglia in paraquat-induced dopaminergic neurotoxicity.
pubmed:affiliation
Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
pubmed:publicationType
Journal Article