Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 32, Pages 10528-10540Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0416-14.2014
Keywords
epilepsy; glutamate; microglia; NMDA receptor; P2Y12 receptor; process extension
Categories
Funding
- National Institutes of Health [R01NS088627]
- American Heart Association [11SDG7340011]
- Michael J. Fox Foundation
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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.
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