PMID- 36550125
OWN - NLM
STAT- MEDLINE
DCOM- 20221226
LR  - 20230119
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Dec 22
TI  - ERK/mTOR signaling may underlying the antidepressant actions of rapastinel in 
      mice.
PG  - 522
LID - 10.1038/s41398-022-02290-5 [doi]
LID - 522
AB  - Rapastinel as the allosteric modulator of N-methyl-D-aspartate receptor (NMDAR) 
      produces rapid antidepressant-like effects dependent on brain-derived 
      neurotrophic factor (BDNF) and VGF (nonacryonimic) release. Herein, we further 
      explore the molecular mechanisms of the antidepressant effects of repeated 
      administration with rapastinel in mice. Our results showed that continuous 3-day 
      rapastinel (5 and 10 mg/kg, i.v.) produced antidepressant-like actions dependent 
      on the increase in extracellular regulated protein kinase (ERK)/mammalian target 
      of rapamycin (mTOR) signaling and downstream substrates p70S6 kinase (p70S6k) and 
      the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which may induce 
      the expression of VGF and BDNF in the hippocampus and prefrontal cortex of mice. 
      Furthermore, compared with a single treatment, our data indicated that 3-day 
      repeated rapastinel treatment produced antidepressant-like actions accompanied by 
      potentiation of ERK/mTOR/VGF/BDNF/tropomyosin-related kinase receptor B (TrkB) 
      signaling. Based on previous and our supplementary data that showed the pivotal 
      role of on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 
      in the rapid release of VGF and BDNF and activation of TrkB by a single dose of 
      rapastinel, we postulate that the antidepressant-like effects of single or 
      repeated administration of rapastinel may result in the rapid release of VGF and 
      BDNF or ERK/mTOR signaling pathway-mediated VGF/BDNF/TrkB autoregulatory feedback 
      loop respectively. Our current work adds new knowledge to the molecular 
      mechanisms that underlie the antidepressant-like actions of rapastinel in mice.
CI  - (c) 2022. The Author(s).
FAU - Shen, Mengxin
AU  - Shen M
AD  - Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo 
      University, 315211, Ningbo, Zhejiang, People's Republic of China.
AD  - School of Basic Medical Science, School of Medicine, Ningbo University, 315211, 
      Ningbo, Zhejiang, People's Republic of China.
AD  - Central Laboratory, Ningbo First Hospital, Zhejiang University, 315010, Ningbo, 
      Zhejiang, China.
FAU - Lv, Dan
AU  - Lv D
AD  - Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo 
      University, 315211, Ningbo, Zhejiang, People's Republic of China.
AD  - School of Basic Medical Science, School of Medicine, Ningbo University, 315211, 
      Ningbo, Zhejiang, People's Republic of China.
FAU - Liu, Xinya
AU  - Liu X
AD  - Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo 
      University, 315211, Ningbo, Zhejiang, People's Republic of China.
AD  - School of Basic Medical Science, School of Medicine, Ningbo University, 315211, 
      Ningbo, Zhejiang, People's Republic of China.
FAU - Wang, Chuang
AU  - Wang C
AUID- ORCID: 0000-0002-3816-230X
AD  - Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo 
      University, 315211, Ningbo, Zhejiang, People's Republic of China. 
      wangchuang@nbu.edu.cn.
AD  - School of Basic Medical Science, School of Medicine, Ningbo University, 315211, 
      Ningbo, Zhejiang, People's Republic of China. wangchuang@nbu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221222
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 6A1X56B95E (GLYX-13 peptide)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Antidepressive Agents)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Brain-Derived Neurotrophic Factor/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Antidepressive Agents/pharmacology/therapeutic use
MH  - Mammals/metabolism
PMC - PMC9780240
COIS- The authors declare no competing interests.
EDAT- 2022/12/23 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/12/22
CRDT- 2022/12/22 23:18
PHST- 2021/12/10 00:00 [received]
PHST- 2022/12/14 00:00 [accepted]
PHST- 2022/12/10 00:00 [revised]
PHST- 2022/12/22 23:18 [entrez]
PHST- 2022/12/23 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/12/22 00:00 [pmc-release]
AID - 10.1038/s41398-022-02290-5 [pii]
AID - 2290 [pii]
AID - 10.1038/s41398-022-02290-5 [doi]
PST - epublish
SO  - Transl Psychiatry. 2022 Dec 22;12(1):522. doi: 10.1038/s41398-022-02290-5.