Linked Life Data

18384650

Source:http://linkedlifedata.com/resource/pubmed/id/18384650

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-7-2
pubmed:abstractText
We investigated the consequences of transient application of specific stimuli mimicking inflammation to hippocampal tissue on microglia activation and neuronal cell vulnerability to a subsequent excitotoxic insult. Two-week-old organotypic hippocampal slice cultures, from 7-day-old C57BL/6 donor mice, were exposed for 3 h to lipopolysaccharide (LPS; 10 ng/mL) followed by 3 h co-incubation with 1 mM ATP, or 100 microM 2'3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate triethylammonium, a selective P2X(7) receptor agonist. These treatments in combination, but not individually, induced a pronounced activation and apoptotic-like death of macrophage antigen-1 (MAC-1)-positive microglia associated with a massive release of interleukin (IL)-1beta exceeding that induced by LPS alone. Antagonists of P2X(7) receptors prevented these effects. Transient pre-exposure of slice cultures to a combination of LPS and P2X(7) receptor agonists, but not either one or the other alone, significantly exacerbated CA3 pyramidal cell loss induced by subsequent 12 h exposure to 8 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazole propinate (AMPA). Potentiation of AMPA toxicity was prevented when IL-1beta production or its receptor signaling were blocked by an inhibitor of interleukin-converting-enzyme or IL-1 receptor antagonist during application of LPS + ATP. The same treatments did not prevent microglia apoptosis-like death. These findings show that transient exposure to specific pro-inflammatory stimuli in brain tissue can prime neuronal susceptibility to a subsequent excitotoxic insult. P2X(7) receptor stimulation, and the consequent IL-1beta release, is mandatory for exacerbation of neuronal loss. These mechanisms may contribute to determine cell death/survival in acute and chronic neurodegenerative conditions associated with inflammatory events.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18384650-Adenosine Triphosphate, pubmed-meshheading:18384650-Animals, pubmed-meshheading:18384650-Apoptosis, pubmed-meshheading:18384650-Drug Synergism, pubmed-meshheading:18384650-Encephalitis, pubmed-meshheading:18384650-Excitatory Amino Acid Agonists, pubmed-meshheading:18384650-Hippocampus, pubmed-meshheading:18384650-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:18384650-Interleukin-1beta, pubmed-meshheading:18384650-Lipopolysaccharides, pubmed-meshheading:18384650-Mice, pubmed-meshheading:18384650-Mice, Inbred C57BL, pubmed-meshheading:18384650-Microglia, pubmed-meshheading:18384650-Nerve Degeneration, pubmed-meshheading:18384650-Neurotoxins, pubmed-meshheading:18384650-Organ Culture Techniques, pubmed-meshheading:18384650-Pyramidal Cells, pubmed-meshheading:18384650-Receptors, Interleukin-1, pubmed-meshheading:18384650-Receptors, Purinergic P2, pubmed-meshheading:18384650-Receptors, Purinergic P2X7
pubmed:year
2008
pubmed:articleTitle
Inflammatory events in hippocampal slice cultures prime neuronal susceptibility to excitotoxic injury: a crucial role of P2X7 receptor-mediated IL-1beta release.
pubmed:affiliation
Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't