Microglial P2Y12 receptor regulates seizure-induced neurogenesis and immature neuronal projections

Mingshu Mo, Ukpong B. Eyo, Manling Xie, Jiyun Peng, Dale B. Bosco, Anthony D. Umpierre, Xiaoqin Zhu, Dai Shi Tian, Pingyi Xu, Long Jun Wu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Seizures are common in humans with various etiologies ranging from congenital aberrations to acute injuries that alter the normal balance of brain excitation and inhibition. A notable consequence of seizures is the induction of aberrant neurogenesis and increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development are not fully understood. Recent studies show that microglia, the brain's resident immune cell, contribute to normal neurogenesis and regulate seizure phenotypes. However, the role of microglia in aberrant neurogenic seizure contexts has not been adequately investigated. To address this question, we coupled the intracerebroventricular kainic acid model with current pharmacogenetic approaches to eliminate microglia in male mice. We show that microglia promote seizure-induced neurogenesis and subsequent seizure-induced immature neuronal projections above and below the pyramidal neurons between the DG and the CA3 regions. Furthermore, we identify microglial P2Y12 receptors (P2Y12R) as a participant in this neurogenic process. Together, our results implicate microglial P2Y12R signaling in epileptogenesis and provide further evidence for targeting microglia in general and microglial P2Y12R in specific to ameliorate proepileptogenic processes

Original languageEnglish (US)
Pages (from-to)9453-9464
Number of pages12
JournalJournal of Neuroscience
Volume39
Issue number47
DOIs
StatePublished - Nov 20 2019

Keywords

  • Immature Projections
  • Microglia
  • Neurogenesis
  • P2Y12R
  • Seizures

ASJC Scopus subject areas

  • Neuroscience(all)

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