PMID- 38307148
OWN - NLM
STAT- MEDLINE
DCOM- 20240311
LR  - 20240311
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 463
DP  - 2024 Apr 12
TI  - Selective disruption of mTORC1 and mTORC2 in VTA astrocytes induces depression 
      and anxiety-like behaviors in mice.
PG  - 114888
LID - S0166-4328(24)00044-5 [pii]
LID - 10.1016/j.bbr.2024.114888 [doi]
AB  - Dysfunction of the mechanistic target of rapamycin (mTOR) signaling pathway is 
      implicated in neuropsychiatric disorders including depression and anxiety. Most 
      studies have been focusing on neurons, and the function of mTOR signaling pathway 
      in astrocytes is less investigated. mTOR forms two distinct complexes, mTORC1 and 
      mTORC2, with key scaffolding protein Raptor and Rictor, respectively. The ventral 
      tegmental area (VTA), a vital component of the brain reward system, is enrolled 
      in regulating both depression and anxiety. In the present study, we aimed to 
      examine the regulation effect of VTA astrocytic mTOR signaling pathway on 
      depression and anxiety. We specifically deleted Raptor or Rictor in VTA 
      astrocytes in mice and performed a series of behavioral tests for depression and 
      anxiety. Deletion of Raptor and Rictor both decreased the immobility time in the 
      tail suspension test and the latency to eat in the novelty suppressed feeding 
      test, and increased the horizontal activity and the movement time in locomotor 
      activity. Deletion of Rictor decreased the number of total arm entries in the 
      elevated plus-maze test and the vertical activity in locomotor activity. These 
      data suggest that VTA astrocytic mTORC1 plays a role in regulating 
      depression-related behaviors and mTORC2 is involved in both depression and 
      anxiety-related behaviors. Our results indicate that VTA astrocytic mTOR 
      signaling pathway might be new targets for the treatment of psychiatric 
      disorders.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Zheng, Ziteng
AU  - Zheng Z
AD  - Department of Psychology, Binzhou Medical University Hospital, the First School 
      of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 256603, 
      China; Medical Research Center, Binzhou Medical University Hospital, the First 
      School of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 
      256603, China.
FAU - Zhou, Han
AU  - Zhou H
AD  - Department of Psychology, Binzhou Medical University Hospital, the First School 
      of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 256603, 
      China; Medical Research Center, Binzhou Medical University Hospital, the First 
      School of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 
      256603, China.
FAU - Yang, Lu
AU  - Yang L
AD  - Department of Psychology, Binzhou Medical University Hospital, the First School 
      of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 256603, 
      China; Medical Research Center, Binzhou Medical University Hospital, the First 
      School of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 
      256603, China.
FAU - Zhang, Lanlan
AU  - Zhang L
AD  - Department of Psychology, Binzhou Medical University Hospital, the First School 
      of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 256603, 
      China.
FAU - Guo, Ming
AU  - Guo M
AD  - Department of Psychology, Binzhou Medical University Hospital, the First School 
      of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 256603, 
      China; Medical Research Center, Binzhou Medical University Hospital, the First 
      School of Clinical Medicine of Binzhou Medical University, Binzhou, Shandong 
      256603, China. Electronic address: byfygm@126.com.
LA  - eng
PT  - Journal Article
DEP - 20240201
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Carrier Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Mechanistic Target of Rapamycin Complex 2/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - *Ventral Tegmental Area/metabolism
MH  - *Astrocytes/metabolism
MH  - Depression
MH  - Multiprotein Complexes/metabolism
MH  - Rapamycin-Insensitive Companion of mTOR Protein/metabolism
MH  - Carrier Proteins/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Regulatory-Associated Protein of mTOR/metabolism
MH  - Transcription Factors/metabolism
MH  - Anxiety
OTO - NOTNLM
OT  - Anxiety
OT  - Astrocyte
OT  - Depression
OT  - MTORC1
OT  - MTORC2
OT  - Ventral tegmental area
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2024/02/03 00:41
MHDA- 2024/03/11 06:42
CRDT- 2024/02/02 19:28
PHST- 2023/12/11 00:00 [received]
PHST- 2024/01/23 00:00 [revised]
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/03/11 06:42 [medline]
PHST- 2024/02/03 00:41 [pubmed]
PHST- 2024/02/02 19:28 [entrez]
AID - S0166-4328(24)00044-5 [pii]
AID - 10.1016/j.bbr.2024.114888 [doi]
PST - ppublish
SO  - Behav Brain Res. 2024 Apr 12;463:114888. doi: 10.1016/j.bbr.2024.114888. Epub 
      2024 Feb 1.