PMID- 36937661
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230321
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 17
DP  - 2023
TI  - Efavirenz restored NMDA receptor dysfunction and inhibited epileptic seizures in 
      GluN2A/Grin2a mutant mice.
PG  - 1086462
LID - 10.3389/fnins.2023.1086462 [doi]
LID - 1086462
AB  - INTRODUCTION: N-methyl-D-aspartate receptor (NMDAR) is one of the main receptor 
      of the excitatory neurotransmitter glutamate in the brain, which is the key 
      determinant of the excitatory/inhibitory balance of neural network. GluN2A/GRIN2A 
      is one of the subunits of NMDAR and plays an important role in epilepsy. 
      Approximately 78% of patients with GluN2A/Grin2a mutations have epilepsy, and the 
      underlying mechanism of this association is not well characterized. METHODS: We 
      constructed a mouse model of hyperthermic seizure, and conducted in vitro and in 
      vivo electrophysiological and behavioral studies to clarify the pathogenic 
      characteristics and mechanism of GluN2A/GRIN2A-V685G mutation. In addition, the 
      drug efavirenz (EFV), which is used to treat HIV infection, was administrated to 
      mutant animals to assess whether it can restore the loss of function. RESULTS: 
      Mutant mice showed no significant change in the mRNA or protein expressions of 
      NMDAR compared with wild type (WT) mice. Mice with GluN2A/GRIN2A-V685G mutation 
      exhibited shorter latency to seizure, increased frequency of seizure-like events, 
      decreased peak current and current area of NMDAR excitatory postsynaptic current, 
      and decreased event frequency of micro-inhibitory postsynaptic current, compared 
      to WT mice. They also exhibited decreased threshold, increased amplitude, 
      increased input resistance, and increased root number of action potential. EFV 
      administration reversed these changes. The loss-of-function (LoF) mutation of 
      NMDAR changed the excitatory/inhibitory balance of neural network, rendering 
      animal more prone to seizures. DISCUSSION: EFV was indicated to hold its 
      potential in the treatment of inherited epilepsy.
CI  - Copyright (c) 2023 Zhao, Zhong, Zhang, Li, Zhou, Fang, Ding and Lin.
FAU - Zhao, Teng
AU  - Zhao T
AD  - Department of Neurology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Zhong, Rui
AU  - Zhong R
AD  - Department of Neurology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Zhang, Xinyue
AU  - Zhang X
AD  - Department of Neurology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Li, Guangjian
AU  - Li G
AD  - Department of Neurology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Zhou, Chunkui
AU  - Zhou C
AD  - Department of Neurology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Fang, Shaokuan
AU  - Fang S
AD  - Department of Neurology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Ding, Ying
AU  - Ding Y
AD  - Department of Radiology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Lin, Weihong
AU  - Lin W
AD  - Department of Neurology, The First Hospital of Jilin University, Changchun, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230302
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC10017539
OTO - NOTNLM
OT  - GluN2A/GRIN2A-V685G mutation
OT  - NMDA receptor
OT  - efavirenz
OT  - epilepsy
OT  - loss of function
OT  - seizure
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/03/21 06:00
MHDA- 2023/03/21 06:01
PMCR- 2023/01/01
CRDT- 2023/03/20 04:07
PHST- 2022/11/01 00:00 [received]
PHST- 2023/02/02 00:00 [accepted]
PHST- 2023/03/20 04:07 [entrez]
PHST- 2023/03/21 06:00 [pubmed]
PHST- 2023/03/21 06:01 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2023.1086462 [doi]
PST - epublish
SO  - Front Neurosci. 2023 Mar 2;17:1086462. doi: 10.3389/fnins.2023.1086462. 
      eCollection 2023.