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https://hdl.handle.net/10316/8397
Título: | Inflammatory events in hippocampal slice cultures prime neuronal susceptibility to excitotoxic injury: a crucial role of P2X<sub>7</sub> receptor-mediated IL-1β release | Autor: | Bernardino, Liliana Balosso, Silvia Ravizza, Teresa Marchi, Nicola Ku, George Randle, John C. Malva, João O. Vezzani, Annamaria |
Data: | 2008 | Citação: | Journal of Neurochemistry. 106:1 (2008) 271-280 | Resumo: | 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 03BCM 2'3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate triethylammonium, a selective P2X7 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)-103B2 exceeding that induced by LPS alone. Antagonists of P2X7 receptors prevented these effects. Transient pre-exposure of slice cultures to a combination of LPS and P2X7 receptor agonists, but not either one or the other alone, significantly exacerbated CA3 pyramidal cell loss induced by subsequent 12 h exposure to 8 03BCM 03B1-amino-3-hydroxy-5-methyl-4-isoxazole propinate (AMPA). Potentiation of AMPA toxicity was prevented when IL-103B2 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. P2X7 receptor stimulation, and the consequent IL-103B2 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. | URI: | https://hdl.handle.net/10316/8397 | DOI: | 10.1111/j.1471-4159.2008.05387.x | Direitos: | openAccess |
Aparece nas coleções: | FMUC Medicina - Artigos em Revistas Internacionais |
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