PMID- 34716784
OWN - NLM
STAT- MEDLINE
DCOM- 20220201
LR  - 20220201
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 239
IP  - 2
DP  - 2022 Feb
TI  - Electroconvulsive seizure inhibits the mTOR signaling pathway via AMPK in the rat 
      frontal cortex.
PG  - 443-454
LID - 10.1007/s00213-021-06015-2 [doi]
AB  - RATIONALE: Accumulating evidence indicates critical involvement of mammalian 
      target of rapamycin (mTOR) in the treatment of depressive disorders, epilepsy, 
      and neurodegenerative disorders through its signal transduction mechanisms 
      related to protein translation, autophagy, and synaptic remodeling. 
      Electroconvulsive seizure (ECS) treatment is a potent antidepressive, 
      anti-convulsive, and neuroprotective therapeutic modality; however, its effects 
      on mTOR signaling have not yet been clarified. METHODS: The effect of ECS on the 
      mTOR complex 1 (mTORC1) pathway was investigated in the rat frontal cortex. ECS 
      or sham treatment was administered once per day for 10 days (E10X or sham), and 
      compound C was administered through the intracerebroventricular cannula. Changes 
      in mTORC1-associated signaling molecules and their interactions were analyzed. 
      RESULTS: E10X reduced phosphorylation of mTOR downstream substrates, including 
      p70S6K, S6, and 4E-BP1, and increased inhibitory phosphorylation of mTOR at 
      Thr2446 compared to the sham group in the rat frontal cortex, indicating 
      E10X-induced inhibition of mTORC1 activity. Akt and ERK1/2, upstream kinases that 
      activate mTORC1, were not inhibited; however, AMPK, which can inhibit mTORC1, was 
      activated. AMPK-responsive phosphorylation of Raptor at Ser792 and TSC2 at 
      Ser1387 inhibiting mTORC1 was increased by E10X. Moreover, intrabrain inhibition 
      of AMPK restored E10X-induced changes in the phosphorylation of S6, Raptor, and 
      TSC2, indicating mediation of AMPK in E10X-induced mTOR inhibition. CONCLUSIONS: 
      Repeated ECS treatments inhibit mTORC1 signaling by interactive crosstalk between 
      mTOR and AMPK pathways, which could play important roles in the action of ECS via 
      autophagy induction.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Kim, Se Hyun
AU  - Kim SH
AUID- ORCID: 0000-0001-7078-2835
AD  - Department of Psychiatry, Seoul National University Hospital, Seoul National 
      University College of Medicine, Seoul, Republic of Korea. sh3491@snu.ac.kr.
FAU - Yu, Hyun Sook
AU  - Yu HS
AD  - Biomedical Research Institute, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Huh, Seonghoo
AU  - Huh S
AD  - Biomedical Research Institute, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Kang, Ung Gu
AU  - Kang UG
AD  - Department of Psychiatry, Seoul National University Hospital, Seoul National 
      University College of Medicine, Seoul, Republic of Korea.
AD  - Institute of Human Behavioral Medicine, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Kim, Yong Sik
AU  - Kim YS
AD  - Department of Psychiatry, NowonEulji Medical Center, Eulji University, Seoul, 
      Republic of Korea.
LA  - eng
GR  - 2017R1D1A1B03035649/ministry of science, information and communication 
      technologies, republic of korea/
GR  - 2020R1F1A1074260/ministry of science, information and communication technologies, 
      republic of korea/
PT  - Journal Article
DEP - 20211030
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - *AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Frontal Lobe/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Seizures
MH  - Signal Transduction
MH  - *TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - AMP-activated protein kinase
OT  - Electroconvulsive therapy
OT  - Mammalian target of rapamycin
EDAT- 2021/10/31 06:00
MHDA- 2022/02/02 06:00
CRDT- 2021/10/30 12:06
PHST- 2021/07/15 00:00 [received]
PHST- 2021/10/13 00:00 [accepted]
PHST- 2021/10/31 06:00 [pubmed]
PHST- 2022/02/02 06:00 [medline]
PHST- 2021/10/30 12:06 [entrez]
AID - 10.1007/s00213-021-06015-2 [pii]
AID - 10.1007/s00213-021-06015-2 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2022 Feb;239(2):443-454. doi: 
      10.1007/s00213-021-06015-2. Epub 2021 Oct 30.