Source:http://linkedlifedata.com/resource/pubmed/id/12421370
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2002-11-7
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| pubmed:abstractText |
The purpose of this study was to assess and compare the toxicity of beta-amyloid (Abeta) on primary cortical and mesencephalic neurons cultured with and without microglia in order to determine the mechanism underlying microglia-mediated Abeta-induced neurotoxicity. Incubation of cortical or mesencephalic neuron-enriched and mixed neuron-glia cultures with Abeta(1-42) over the concentration range 0.1-6.0 microm caused concentration-dependent neurotoxicity. High concentrations of Abeta (6.0 microm for cortex and 1.5-2.0 microm for mesencephalon) directly injured neurons in neuron-enriched cultures. In contrast, lower concentrations of Abeta (1.0-3.0 microm for cortex and 0.25-1.0 microm for mesencephalon) caused significant neurotoxicity in mixed neuron-glia cultures, but not in neuron- enriched cultures. Several lines of evidence indicated that microglia mediated the potentiated neurotoxicity of Abeta, including the observations that low concentrations of Abeta activated microglia morphologically in neuron-glia cultures and that addition of microglia to cortical neuron-glia cultures enhanced Abeta-induced neurotoxicity. To search for the mechanism underlying the microglia-mediated effects, several proinflammatory factors were examined in neuron-glia cultures. Low doses of Abeta significantly increased the production of superoxide anions, but not of tumor necrosis factor-alpha, interleukin-1beta or nitric oxide. Catalase and superoxide dismutase significantly protected neurons from Abeta toxicity in the presence of microglia. Inhibition of NADPH oxidase activity by diphenyleneiodonium also prevented Abeta-induced neurotoxicity in neuron-glia mixed cultures. The role of NADPH oxidase-generated superoxide in mediating Abeta-induced neurotoxicity was further substantiated by a study which showed that Abeta caused less of a decrease in dopamine uptake in mesencephalic neuron-glia cultures from NADPH oxidase-deficient mutant mice than in that from wild-type controls. This study demonstrates that one of the mechanisms by which microglia can enhance the neurotoxicity of Abeta is via the production of reactive oxygen species.
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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/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Catalase,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0022-3042
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
83
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
973-83
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:12421370-Amyloid beta-Peptides,
pubmed-meshheading:12421370-Animals,
pubmed-meshheading:12421370-Catalase,
pubmed-meshheading:12421370-Cells, Cultured,
pubmed-meshheading:12421370-Cerebral Cortex,
pubmed-meshheading:12421370-Coculture Techniques,
pubmed-meshheading:12421370-Enzyme Inhibitors,
pubmed-meshheading:12421370-Interleukin-1,
pubmed-meshheading:12421370-Mesencephalon,
pubmed-meshheading:12421370-Mice,
pubmed-meshheading:12421370-Mice, Inbred C57BL,
pubmed-meshheading:12421370-Microglia,
pubmed-meshheading:12421370-NADPH Oxidase,
pubmed-meshheading:12421370-Neurons,
pubmed-meshheading:12421370-Neuroprotective Agents,
pubmed-meshheading:12421370-Nitric Oxide,
pubmed-meshheading:12421370-Rats,
pubmed-meshheading:12421370-Rats, Inbred F344,
pubmed-meshheading:12421370-Reactive Oxygen Species,
pubmed-meshheading:12421370-Superoxide Dismutase,
pubmed-meshheading:12421370-Superoxides,
pubmed-meshheading:12421370-Tumor Necrosis Factor-alpha
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| pubmed:year |
2002
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| pubmed:articleTitle |
Microglia enhance beta-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species.
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| pubmed:affiliation |
Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. qin1@niehs.nih.gov
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| pubmed:publicationType |
Journal Article
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