Neuroprotective effects of microglial P2Y1 receptors against ischemic neuronal injury

Yuichiro Fukumoto, Kenji Tanaka, Bijay Parajuli, Keisuke Shibata, Hideyuki Yoshioka, Kazuya Kanemaru, Christian Gachet, Kazuhiro Ikenaka, Schuichi Koizumi, Hiroyuki Kinouchi

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7 Citations (Scopus)

Abstract

Extracellular ATP, which is released from damaged cells after ischemia, activates P2 receptors. P2Y1 receptors (P2Y1R) 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 P2Y1R 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 P2Y1R to provide neuroprotective effects following ischemic stress. Cerebral ischemia resulted in increased microglial P2Y1R expression. The number of injured hippocampal neurons was significantly higher in P2Y1 R knockout (KO) mice than wildtype mice after forebrain ischemia. Propidium iodide (PI) uptake, a marker for dying cells, was significantly higher in P2Y1R 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 P2Y1R in microglia. In summary, these data suggest that microglial P2Y1R mediate neuroprotective effects against ischemic stress and OGD insult.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Keywords

  • ATP
  • brain ischemia
  • calcium imaging
  • microglia
  • neuroprotection

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Fukumoto, Y., Tanaka, K., Parajuli, B., Shibata, K., Yoshioka, H., Kanemaru, K., Gachet, C., Ikenaka, K., Koizumi, S., & Kinouchi, H. (Accepted/In press). Neuroprotective effects of microglial P2Y1 receptors against ischemic neuronal injury. Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X18805317