Journal article
P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation
Neuropharmacology, Vol.73, pp.311-319
10/2013
DOI: 10.1016/j.neuropharm.2013.05.032
PMCID: PMC3786777
PMID: 23770338
Abstract
Brain-resident microglia may promote tissue repair following stroke but, like other cells, they are vulnerable to ischemia. Here we identify mechanisms involved in microglial ischemic vulnerability. Using time-lapse imaging of cultured BV2 microglia, we show that simulated ischemia (oxygen-glucose deprivation; OGD) induces BV2 microglial cell death. Removal of extracellular Ca2+ or application of Brilliant Blue G (BBG), a potent P2X7 receptor (P2X7R) antagonist, protected BV2 microglia from death. To validate and extend these in vitro findings, we assessed parenchymal microglia in freshly isolated hippocampal tissue slices from GFP-reporter mice (CX3CR1GFP/+). We confirmed that calcium removal or application of apyrase, an ATP-degrading enzyme, abolished OGD-induced microglial cell death in situ, consistent with involvement of ionotropic purinergic receptors. Indeed, whole cell recordings identified P2X7R-like currents in tissue microglia, and OGD-induced microglial cell death was inhibited by BBG. These pharmacological results were complemented by studies in tissue slices from P2X7R null mice, in which OGD-induced microglia cell death was reduced by nearly half. Together, these results indicate that stroke-like conditions induce calcium-dependent microglial cell death that is mediated in part by P2X7R. This is the first identification of a purinergic receptor regulating microglial survival in living brain tissues. From a therapeutic standpoint, these findings could help direct novel approaches to enhance microglial survival and function following stroke and other neuropathological conditions.
•Oxygen-glucose deprivation (OGD) induces calcium-dependent microglial cell death.•OGD-induced microglial cell death is regulated by extracellular purines.•Neonatal microglia in situ express P2X7 receptor-like currents.•Disruption of P2X7 receptors significantly reduces OGD-induced death of microglia.
Details
- Title: Subtitle
- P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation
- Creators
- Ukpong B Eyo - Department of Biology, University of Iowa, 369 Biology Building, Iowa City, IA 52242, USASam A Miner - Department of Biology, University of Iowa, 369 Biology Building, Iowa City, IA 52242, USAKatelin E Ahlers - Department of Biology, University of Iowa, 369 Biology Building, Iowa City, IA 52242, USALong-Jun Wu - Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USAMichael E Dailey - Department of Biology, University of Iowa, 369 Biology Building, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.73, pp.311-319
- DOI
- 10.1016/j.neuropharm.2013.05.032
- PMID
- 23770338
- PMCID
- PMC3786777
- NLM abbreviation
- Neuropharmacology
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000968, name: American Heart Association, award: 0950160G; name: NIH, award: NS064006; name: Iowa Center for Molecular Auditory Neuroscience, award: DC010362
- Language
- English
- Date published
- 10/2013
- Academic Unit
- Iowa Neuroscience Institute; Biology; Neuroscience and Pharmacology
- Record Identifier
- 9983992064402771
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