Linked Life Data

1355433

Source:http://linkedlifedata.com/resource/pubmed/id/1355433

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1992-10-7
pubmed:abstractText
The co-localization of activated macrophages and damaged neurons observed in brain injury and degenerative brain diseases may hint to macrophage-induced neuronal cytotoxicity. Recently, macrophages have been found to secrete neurotoxic molecules such as radical oxygen intermediates and glutamate, the latter interacting with N-methyl-D-aspartate (NMDA) receptors. As shown in the present study, brain macrophages termed microglial cells co-cultured with differentiated cerebellar neurons excert potent neurotoxic effects. Neurotoxicity is unlikely to be due to cytokines since tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and interferon (IFN)-alpha/IFN-beta/IFN-gamma had no such effects. In contrast, when treating neurons with H2O2 or oxygen radical-generating systems cytotoxicity was induced. Furthermore, microglia were found to produce O2- and H2O2 when triggered with phorbol 12-myristate 13-acetate. However, in co-cultures of neurons and microglia, oxygen-radical scavengers catalase and superoxide dismutase, failed to protect neurons from microglia-induced killing. Moreover, when using undifferentiated neurons which are susceptible to H2O2 but not to NMDA receptor-dependent killing, microglia did not destroy the neurons. Thus, the amount of reactive oxygen intermediates produced by microglia in co-culture do not reach the critical concentrations required for neurotoxicity. As dibenzocyclohepteneimide, an antagonist to NMDA receptors neutralized neurotoxicity in microglia-neuronal co-cultures, excitatory amino acids released by microglia are suggested to compose the major determinant of neurotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2429-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Macrophage-induced cytotoxicity of N-methyl-D-aspartate receptor positive neurons involves excitatory amino acids rather than reactive oxygen intermediates and cytokines.
pubmed:affiliation
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't