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- Title
Neuronal Hyperactivity Recruits Microglial Processes via Neuronal NMDA Receptors and Microglial P2Y12 Receptors after Status Epilepticus.
- Authors
Eyo, Ukpong B.; Peng, Jiyun; Swiatkowski, Przemyslaw; Mukherjee, Aparna; Bispo, Ashley; Wu, Long-Jun
- 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 ofthe glutamate-induced microglialprocess 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.
- Subjects
NEURONS; MICROGLIA; METHYL aspartate receptors; STATUS epilepticus; HIPPOCAMPUS (Brain); ADENOSINE triphosphate
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 32, p10528
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0416-14.2014