Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy

Cell Reports
Xiaofeng ZhaoYunfei Huang

Abstract

Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention.

Citations

Feb 13, 2019·International Journal of Molecular Sciences·Shaip Krasniqi, Armond Daci
Dec 4, 2019·Epilepsy Currents·Season K Wyatt-Johnson, Amy L Brewster
Feb 11, 2020·Annals of the New York Academy of Sciences·Marson PutraThimmasettappa Thippeswamy
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May 7, 2021·Epilepsia·Zhou WuChristian Steinhäuser

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Datasets Mentioned

BETA
GSE108625

Methods Mentioned

BETA
surgical resections
FACS
RNA-seq
GTPase
Assay
PCR

Software Mentioned

iPathwayGuider
GraphPad Prism5
iPathway Guide
Advaita
GraphPad Prism

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