PMID- 35309681
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220322
IS  - 1662-5153 (Print)
IS  - 1662-5153 (Electronic)
IS  - 1662-5153 (Linking)
VI  - 16
DP  - 2022
TI  - The Regulation of Glutamate Transporter 1 in the Rapid Antidepressant-Like Effect 
      of Ketamine in Mice.
PG  - 789524
LID - 10.3389/fnbeh.2022.789524 [doi]
LID - 789524
AB  - Accumulating evidence suggests that glutamate clearance plays a critical role in 
      the pathophysiology and treatment of depression. Preclinical and clinical studies 
      have demonstrated that ketamine provides an immediate and sustained 
      antidepressant effect. However, the precise mechanism of its action remains to be 
      elucidated. Glutamate transporter 1 (GLT1) participates in glutamate clearance; 
      therefore, we hypothesized that GLT1 may play an important role in the 
      antidepressant effect of ketamine. In this study, we determined that GLT1 
      inhibition blocks the antidepressant-like properties of ketamine and alters the 
      phosphorylation of the mammalian target of rapamycin (mTOR) in the prefrontal 
      cortex (PFC). Our results show that pretreatment with dihydrokainic acid (DHK), a 
      GLT1 inhibitor, alleviated the antidepressant-like effect of ketamine, and 
      decreased the level of phosphorylated mTOR (pmTOR) in mice (which is normally 
      upregulated by ketamine). In addition, inhibition of 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor and L-type 
      voltage-dependent calcium channel (L-VDCC) significantly abolished the 
      antidepressant-like effect of ketamine. Moreover, inhibition of L-VDCC 
      significantly blocked the upregulation of GLT1 and BDNF in the PFC of mice. The 
      inhibition of the AMPA receptor only significantly alleviated BDNF. Our results 
      provide insight into the role of GLT1 as the critical presynaptic molecule 
      participating in the pathophysiological mechanism of depression and contributing 
      to the antidepressant-like effect of ketamine. In addition, our study confirms 
      that both AMPA receptor and L-VDCC are crucial factors in the immediate 
      antidepressant-like effect of ketamine.
CI  - Copyright (c) 2022 Chen, Shen, Liu, Xu and Wang.
FAU - Chen, Yaping
AU  - Chen Y
AD  - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School 
      of Medicine, Ningbo, China.
AD  - School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
AD  - College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 
      China.
FAU - Shen, Mengxin
AU  - Shen M
AD  - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School 
      of Medicine, Ningbo, China.
FAU - Liu, Xu
AU  - Liu X
AD  - Department of Pharmacy, General Hospital of Chinese People's Armed Police Forces, 
      Beijing, China.
FAU - Xu, Jiangping
AU  - Xu J
AD  - School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
FAU - Wang, Chuang
AU  - Wang C
AD  - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School 
      of Medicine, Ningbo, China.
LA  - eng
PT  - Journal Article
DEP - 20220302
PL  - Switzerland
TA  - Front Behav Neurosci
JT  - Frontiers in behavioral neuroscience
JID - 101477952
PMC - PMC8926310
OTO - NOTNLM
OT  - L-type voltage-dependent calcium channel
OT  - depression
OT  - glutamate transporter 1
OT  - ketamine
OT  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
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- 2022/03/22 06:00
MHDA- 2022/03/22 06:01
PMCR- 2022/01/01
CRDT- 2022/03/21 08:53
PHST- 2021/10/05 00:00 [received]
PHST- 2022/01/17 00:00 [accepted]
PHST- 2022/03/21 08:53 [entrez]
PHST- 2022/03/22 06:00 [pubmed]
PHST- 2022/03/22 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnbeh.2022.789524 [doi]
PST - epublish
SO  - Front Behav Neurosci. 2022 Mar 2;16:789524. doi: 10.3389/fnbeh.2022.789524. 
      eCollection 2022.