P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation

Ukpong B. Eyo, Sam A. Miner, Katelin E. Ahlers, Long Jun Wu, Michael E. Dailey

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)311-319
Number of pages9
JournalNeuropharmacology
Volume73
DOIs
StatePublished - Jan 1 2013

Keywords

  • ATP
  • Cell death
  • Microglia
  • OGD
  • P2X7
  • Stroke

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation'. Together they form a unique fingerprint.

  • Cite this