P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation.
P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation.
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DOI：
10.1016/j.neuropharm.2013.05.032
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发表时间：
2013-10
影响因子：
4.7
通讯作者：
Dailey ME
中科院分区：
文献类型：
--
作者：
Eyo UB;Miner SA;Ahlers KE;Wu LJ;Dailey ME
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.
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影响因子：
4.7
作者：
Frenguelli BG;Wigmore G;Llaudet E;Dale N
通讯作者：
Dale N
DOI：
10.1523/jneurosci.2102-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Vexler ZS
影响因子：
3.3
作者：
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通讯作者：
Watters, JJ
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
9.3
作者：
Chu K;Yin B;Wang J;Peng G;Liang H;Xu Z;Du Y;Fang M;Xia Q;Luo B
通讯作者：
Luo B