Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus

Ukpong B. Eyo, Jiyun Peng, Przemyslaw Swiatkowski, Aparna Mukherjee, Ashley Bispo, LongJun Wu

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Microglia are highly dynamic immune cells of the CNS and their dynamism is proposed to be regulated by neuronal activities. However, the mechanisms underlying neuronal regulation of microglial dynamism have not been determined. Here, we found an increased number of microglial primary processes in the hippocampus during KA-induced seizure activity. Consistently, global glutamate induced robust microglial process extension toward neurons in both brain slices and in the intact brain in vivo. The mechanism of the glutamate-induced microglial process extension involves the activation of neuronal NMDA receptors, calcium influx, subsequent ATP release, and microglial response through P2Y12 receptors. Seizure-induced increases in microglial process numbers were also dependent on NMDA receptor activation. Finally, we found that P2Y12 KO mice exhibited reduced seizure-induced increases in microglial process numbers and worsened KA-induced seizure behaviors. Our results elucidate the molecular mechanisms underlying microglia-neuron communication that may be potentially neuroprotective in the epileptic brain.

Original languageEnglish (US)
Pages (from-to)10528-10540
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number32
DOIs
StatePublished - Aug 6 2014
Externally publishedYes

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Keywords

  • Epilepsy
  • Glutamate
  • Microglia
  • NMDA receptor
  • P2Y12 receptor
  • Process extension

ASJC Scopus subject areas

  • Neuroscience(all)

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