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Downregulation of P2X 7 receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia
Author(s) -
Wang LiYan,
Cai WenQin,
Chen PengHui,
Deng QiYue,
Zhao CongMin
Publication year - 2009
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20758
Subject(s) - downregulation and upregulation , oligodendrocyte , hypoxia (environmental) , western blot , biology , ischemia , extracellular , receptor , antagonist , intracellular , in vivo , medicine , neuroscience , endocrinology , microbiology and biotechnology , chemistry , biochemistry , central nervous system , oxygen , myelin , organic chemistry , gene
Oligodendrocyte precursor cells (OPCs) are the predominant oligodendrocyte‐lineage stage in the cerebral hemispheres of neonatal rat. Prior studies have shown that OPCs are highly vulnerable to hypoxic‐ischemic injury, yet the mechanisms are not well understood. P2X 7 receptor (P2X 7 R) is an ATP‐gated ion channel that has unusual properties and plays very complex roles in a variety of neuropathologic conditions. However, little is known about the involvement of P2X 7 R in OPCs development and injury. The present study was aimed at examining the presence of P2X 7 R in OPCs and evaluating the change of the receptor expression after hypoxia ischemia. Using Immunofluorescence, RT‐PCR, and western blot analysis, we demonstrated that OPCs expressed P2X 7 R in vitro and in vivo . Activation of P2X 7 R in OPCs in response to 3′‐ O ‐(4‐benzoyl) benzoyl‐ATP (BzATP) led to an increased mobilization of intracellular calcium [Ca 2+ ]i, formation of large pores and cell death. These functional responses were sensitive to pretreatment of cells with the P2X 7 R antagonist, Brilliant Blue G (BBG, 100 nM), which was a selective antagonist for P2X 7 R in nanomole range. A decrease in P2X 7 R expression was observed in cultured OPCs after exposure to oxygen‐glucose deprivation (OGD) for 2 h in vitro . Using a neonatal hypoxic‐ischemic injury model in postnatal 3 rats, the similar downregulation was also detected in ischemic cerebral cortex, subcortical white matter and hippocampus compared with sham operation controls. In conclusion, the present data demonstrated that OPCs expressed functional P2X 7 R. The post‐ischemic downregulation of P2X 7 R suggested a role for this receptor in the pathophysiology of hypoxic‐ischemic brain injury. © 2008 Wiley‐Liss, Inc.