Seizure progression triggered by IQSEC3 loss is mitigated by reducing activated microglia in mice.

Abstract:

:IQSEC3, a guanine nucleotide exchange factor for ADP-ribosylation factors (ARF-GEFs) is specifically expressed at GABAergic synapses, and its loss increases seizure susceptibility in mice. However, the contribution of microglia to initiation and/or progression of seizures in IQSEC3-deficient mice has not been investigated. In the current study, we show that mice with hippocampal dentate gyrus (DG)-specific IQSEC3 knockdown (KD) exhibit microglial activation and death of DG granule cell. Furthermore, treatment of IQSEC3-KD mice with minocycline, an inhibitor of microglial activation, blocks DG granule neuron cell death and the occurrence of spontaneous seizures without affecting GABAergic synapse deficits or loss of somatostatin. Our results suggest that microglial activation is involved in a subset of IQSEC3-KD-induced epileptogenesis stages, and that its regulation could be an alternative strategy for managing epilepsy.

journal_name

Glia

journal_title

Glia

authors

Park D,Kim S,Kim H,Shin J,Jung H,Um JW

doi

10.1002/glia.23876

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

2661-2673

issue

12

eissn

0894-1491

issn

1098-1136

journal_volume

68

pub_type

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