Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy

作者：Zhao Xiaofeng; Liao Yuan; Morgan Shannon; Mathur Ramkumar; Feustel Paul; Mazurkiewicz Joseph; Qian Jiang; Chang Julia; Mathern Gary W; Adamo Matthew A; Ritaccio Anthony L; Gruenthal Michael; Zhu Xinjun; Huang Yunfei^*

来源：Cell Reports, 2018, 22(8): 2080-2093.

DOI：10.1016/j.celrep.2018.02.004

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.

• 出版日期2018-2-20