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

研究成果: Article

8 引用 (Scopus)


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.

ジャーナルJournal of Cerebral Blood Flow and Metabolism
出版物ステータスAccepted/In press - 2018 1 1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

フィンガープリント Neuroprotective effects of microglial P2Y<sub>1</sub> receptors against ischemic neuronal injury' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Fukumoto, Y., Tanaka, K., Parajuli, B., Shibata, K., Yoshioka, H., Kanemaru, K., Gachet, C., Ikenaka, K., Koizumi, S., & Kinouchi, H. (受理済み/印刷中). Neuroprotective effects of microglial P2Y1 receptors against ischemic neuronal injury. Journal of Cerebral Blood Flow and Metabolism.