Downregulation of P2X7 receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia.
Glia
; 57(3): 307-19, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-18942747
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
/
Oligodendroglia
/
Receptores Purinérgicos P2
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Hipóxia-Isquemia Encefálica
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Células-Tronco Adultas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article