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

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Purinergic P2X7 Receptors
Microglia
Cell Death
Oxygen
Glucose
Purinergic Receptors
Stroke
Ischemia
Time-Lapse Imaging
Apyrase
Calcium
Brain
Patch-Clamp Techniques
Adenosine Triphosphate
Pharmacology
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation. / Eyo, Ukpong B.; Miner, Sam A.; Ahlers, Katelin E.; Wu, LongJun; Dailey, Michael E.

In: Neuropharmacology, Vol. 73, 01.01.2013, p. 311-319.

Research output: Contribution to journalArticle

Eyo, Ukpong B. ; Miner, Sam A. ; Ahlers, Katelin E. ; Wu, LongJun ; Dailey, Michael E. / P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation. In: Neuropharmacology. 2013 ; Vol. 73. pp. 311-319.
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