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Publication : Microglial Displacement of GABAergic Synapses Is a Protective Event during Complex Febrile Seizures.

First Author  Wan Y Year  2020
Journal  Cell Rep Volume  33
Issue  5 Pages  108346
PubMed ID  33147450 Mgi Jnum  J:300613
Mgi Id  MGI:6488861 Doi  10.1016/j.celrep.2020.108346
Citation  Wan Y, et al. (2020) Microglial Displacement of GABAergic Synapses Is a Protective Event during Complex Febrile Seizures. Cell Rep 33(5):108346
abstractText  Complex febrile seizures (FSs) lead to a high risk of intractable temporal lobe epilepsy during adulthood, yet the pathological process of complex FSs is largely unknown. Here, we demonstrate that activated microglia extensively associated with glutamatergic neuronal soma displace surrounding GABAergic presynapses in complex FSs. Patch-clamp electrophysiology establishes that the microglial displacement of GABAergic presynapses abrogates a complex-FS-induced increase in GABAergic neurotransmission and neuronal excitability, whereas GABA exerts an excitatory action in this immature stage. Pharmacological inhibition of microglial displacement of GABAergic presynapses or selective ablation of microglia in CD11b(DTR) mice promotes the generation of complex FSs. Blocking or deleting the P2Y12 receptor (P2Y12R) reduces microglial displacement of GABAergic presynapses and shortens the latency of complex FSs. Together, microglial displacement of GABAergic presynapses, regulated by P2Y12R, reduces neuronal excitability to mitigate the generation of complex FSs. Microglial displacement is a protective event during the pathological process of complex FSs.
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