Knockout of the P2Y6 Receptor Prevents Peri-Infarct Neuronal Loss after Transient, Focal Ischemia in Mouse Brain

被引：11

作者：

Milde, Stefan ^{[1
]}

Brown, Guy C. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 04期

基金：

英国医学研究理事会;

关键词：

stroke; ischemia; microglia; phagocytosis; cell death; phagoptosis; neuronal death; delayed neuronal death; selective neuronal loss; MICROGLIAL PHAGOCYTOSIS; STROKE; DEATH; INHIBITION;

D O I：

10.3390/ijms23042304

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

After stroke, there is a delayed neuronal loss in brain areas surrounding the infarct, which may in part be mediated by microglial phagocytosis of stressed neurons. Microglial phagocytosis of stressed or damaged neurons can be mediated by UDP released from stressed neurons activating the P2Y(6) receptor on microglia, inducing microglial phagocytosis of such neurons. We show evidence here from a small trial that the knockout of the P2Y(6) receptor, required for microglial phagocytosis of neurons, prevents the delayed neuronal loss after transient, focal brain ischemia induced by endothelin-1 injection in mice. Wild-type mice had neuronal loss and neuronal nuclear material within microglia in peri-infarct areas. P2Y(6) receptor knockout mice had no significant neuronal loss in peri-infarct brain areas seven days after brain ischemia. Thus, delayed neuronal loss after stroke may in part be mediated by microglial phagocytosis of stressed neurons, and the P2Y(6) receptor is a potential treatment target to prevent peri-infarct neuronal loss.

引用

页数：8