Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus

Lijie Feng, Madhuvika Murugan, Dale B. Bosco, Yong Liu, Jiyun Peng, Gregory A. Worrell, Hai Long Wang, Lauren E. Ta, Jason R. Richardson, Yuxian Shen, Long Jun Wu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Microglial activation has been recognized as a major contributor to inflammation of the epileptic brain. Seizures are commonly accompanied by remarkable microgliosis and loss of neurons. In this study, we utilize the CX3CR1GFP/+ CCR2RFP/+ genetic mouse model, in which CX3CR1+ resident microglia and CCR2+ monocytes are labeled with GFP and RFP, respectively. Using a combination of time-lapse two-photon imaging and whole-cell patch clamp recording, we determined the distinct morphological, dynamic, and electrophysiological characteristics of infiltrated monocytes and resident microglia, and the evolution of their behavior at different time points following kainic acid-induced seizures. Seizure activated microglia presented enlarged somas with less ramified processes, whereas, infiltrated monocytes were smaller, highly motile cells that lacked processes. Moreover, resident microglia, but not infiltrated monocytes, proliferate locally in the hippocampus after seizure. Microglial proliferation was dependent on the colony-stimulating factor 1 receptor (CSF-1R) pathway. Pharmacological inhibition of CSF-1R reduced seizure-induced microglial proliferation, which correlated with attenuation of neuronal death without altering acute seizure behaviors. Taken together, we demonstrated that proliferation of activated resident microglia contributes to neuronal death in the hippocampus via CSF-1R after status epilepticus, providing potential therapeutic targets for neuroprotection in epilepsy.

Original languageEnglish (US)
Pages (from-to)1434-1448
Number of pages15
JournalGlia
Volume67
Issue number8
DOIs
StatePublished - Aug 2019

Keywords

  • colony stimulating factor 1 receptor
  • epilepsy
  • infiltration
  • microglia
  • monocytes
  • proliferation

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Feng, L., Murugan, M., Bosco, D. B., Liu, Y., Peng, J., Worrell, G. A., Wang, H. L., Ta, L. E., Richardson, J. R., Shen, Y., & Wu, L. J. (2019). Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus. Glia, 67(8), 1434-1448. https://doi.org/10.1002/glia.23616