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Publication : Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.

First Author  Zhao X Year  2018
Journal  Cell Rep Volume  22
Issue  8 Pages  2080-2093
PubMed ID  29466735 Mgi Jnum  J:264868
Mgi Id  MGI:6198893 Doi  10.1016/j.celrep.2018.02.004
Citation  Zhao X, et al. (2018) Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy. Cell Rep 22(8):2080-2093
abstractText  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.
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