Abstract:
: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 CD11bDTR 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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Wan Y,Feng B,You Y,Yu J,Xu C,Dai H,Trapp BD,Shi P,Chen Z,Hu Wdoi
10.1016/j.celrep.2020.108346subject
Has Abstractpub_date
2020-11-03 00:00:00pages
108346issue
5issn
2211-1247pii
S2211-1247(20)31335-8journal_volume
33pub_type
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