Please use this identifier to cite or link to this item:
|Title:||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||Authors:||Bernardino, Liliana
Randle, John C.
Malva, João O.
|Issue Date:||2008||Citation:||Journal of Neurochemistry. 106:1 (2008) 271-280||Abstract:||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:||http://hdl.handle.net/10316/8397||DOI:||10.1111/j.1471-4159.2008.05387.x||Rights:||openAccess|
|Appears in Collections:||FMUC Medicina - Artigos em Revistas Internacionais|
Show full item record
checked on Feb 18, 2020
WEB OF SCIENCETM
checked on Aug 2, 2022
Page view(s) 50406
checked on Oct 6, 2022
checked on Oct 6, 2022
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.