Neuroprotective effects of microglial P2Y receptors against ischemic neuronal injury.
Fiche publication
Date publication
octobre 2018
Journal
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GACHET Christian
Tous les auteurs :
Fukumoto Y, Tanaka KF, Parajuli B, Shibata K, Yoshioka H, Kanemaru K, Gachet C, Ikenaka K, Koizumi S, Kinouchi H
Lien Pubmed
Résumé
Extracellular ATP, which is released from damaged cells after ischemia, activates P2 receptors. P2Y receptors (P2YR) have received considerable attention, especially in astrocytes, because their activation plays a central role in the regulation of neuron-to-glia communication. However, the functions or even existence of P2YR in microglia remain unknown, despite the fact that many microglial P2 receptors are involved in several brain diseases. Herein, we demonstrate the presence and functional capability of microglial P2YR to provide neuroprotective effects following ischemic stress. Cerebral ischemia resulted in increased microglial P2YR expression. The number of injured hippocampal neurons was significantly higher in P2Y R knockout (KO) mice than wildtype mice after forebrain ischemia. Propidium iodide (PI) uptake, a marker for dying cells, was significantly higher in P2YR KO hippocampal slices compared with wildtype hippocampal slices at 48 h after 40-min oxygen-glucose deprivation (OGD). Furthermore, increased PI uptake following OGD was rescued by ectopic overexpression of P2YR in microglia. In summary, these data suggest that microglial P2YR mediate neuroprotective effects against ischemic stress and OGD insult.
Mots clés
ATP, brain ischemia, calcium imaging, microglia, neuroprotection
Référence
J. Cereb. Blood Flow Metab.. 2018 Oct 18;:271678X18805317