PMID- 32645240
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 68
IP  - 12
DP  - 2020 Dec
TI  - Seizure progression triggered by IQSEC3 loss is mitigated by reducing activated 
      microglia in mice.
PG  - 2661-2673
LID - 10.1002/glia.23876 [doi]
AB  - 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.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Park, Dongseok
AU  - Park D
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), Daegu, South Korea.
FAU - Kim, Seungjoon
AU  - Kim S
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), Daegu, South Korea.
FAU - Kim, Hyeonho
AU  - Kim H
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), Daegu, South Korea.
FAU - Shin, Jungsu
AU  - Shin J
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), Daegu, South Korea.
FAU - Jung, Hyeji
AU  - Jung H
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), Daegu, South Korea.
FAU - Um, Ji Won
AU  - Um JW
AUID- ORCID: 0000-0002-9355-7726
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), Daegu, South Korea.
AD  - Core Protein Resources Center, DGIST, Daegu, South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200709
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Iqsec3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Dentate Gyrus
MH  - Guanine Nucleotide Exchange Factors
MH  - Hippocampus
MH  - Mice
MH  - *Microglia
MH  - Neurons
MH  - *Seizures
MH  - Synapses
OTO - NOTNLM
OT  - GABA
OT  - IQSEC3
OT  - inhibitory synapse
OT  - microglia
OT  - minocycline
OT  - seizure
EDAT- 2020/07/10 06:00
MHDA- 2021/12/15 06:00
CRDT- 2020/07/10 06:00
PHST- 2020/03/23 00:00 [received]
PHST- 2020/05/29 00:00 [revised]
PHST- 2020/06/04 00:00 [accepted]
PHST- 2020/07/10 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/07/10 06:00 [entrez]
AID - 10.1002/glia.23876 [doi]
PST - ppublish
SO  - Glia. 2020 Dec;68(12):2661-2673. doi: 10.1002/glia.23876. Epub 2020 Jul 9.