PMID- 36045116
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20221117
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Aug 31
TI  - The trilateral interactions between mammalian target of rapamycin (mTOR) 
      signaling, the circadian clock, and psychiatric disorders: an emerging model.
PG  - 355
LID - 10.1038/s41398-022-02120-8 [doi]
LID - 355
AB  - Circadian (~24 h) rhythms in physiology and behavior are evolutionarily conserved 
      and found in almost all living organisms. The rhythms are endogenously driven by 
      daily oscillatory activities of so-called "clock genes/proteins", which are 
      widely distributed throughout the mammalian brain. Mammalian (mechanistic) target 
      of rapamycin (mTOR) signaling is a fundamental intracellular signal transduction 
      cascade that controls important neuronal processes including neurodevelopment, 
      synaptic plasticity, metabolism, and aging. Dysregulation of the mTOR pathway is 
      associated with psychiatric disorders including autism spectrum disorders (ASD) 
      and mood disorders (MD), in which patients often exhibit disrupted daily 
      physiological rhythms and abnormal circadian gene expression in the brain. Recent 
      work has found that the activities of mTOR signaling are temporally controlled by 
      the circadian clock and exhibit robust circadian oscillations in multiple 
      systems. In the meantime, mTOR signaling regulates fundamental properties of the 
      central and peripheral circadian clocks, including period length, entrainment, 
      and synchronization. Whereas the underlying mechanisms remain to be fully 
      elucidated, increasing clinical and preclinical evidence support significant 
      crosstalk between mTOR signaling, the circadian clock, and psychiatric disorders. 
      Here, we review recent progress in understanding the trilateral interactions and 
      propose an "interaction triangle" model between mTOR signaling, the circadian 
      clock, and psychiatric disorders (focusing on ASD and MD).
CI  - (c) 2022. The Author(s).
FAU - Singla, Rubal
AU  - Singla R
AD  - Department of Biomedical Sciences, University of Minnesota Medical School, 
      Duluth, MN, 55812, USA.
FAU - Mishra, Abhishek
AU  - Mishra A
AD  - Department of Biomedical Sciences, University of Minnesota Medical School, 
      Duluth, MN, 55812, USA.
FAU - Cao, Ruifeng
AU  - Cao R
AUID- ORCID: 0000-0001-5105-7726
AD  - Department of Biomedical Sciences, University of Minnesota Medical School, 
      Duluth, MN, 55812, USA. rcao@umn.edu.
AD  - Department of Neuroscience, University of Minnesota Medical School, Minneapolis, 
      MN, 55455, USA. rcao@umn.edu.
LA  - eng
GR  - R01 GM143260/GM/NIGMS NIH HHS/United States
GR  - R01 NS118026/NS/NINDS NIH HHS/United States
GR  - 118026/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20220831
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Circadian Clocks/genetics
MH  - Circadian Rhythm/physiology
MH  - Humans
MH  - *Mental Disorders/genetics
MH  - Signal Transduction/physiology
MH  - *TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC9433414
COIS- The authors declare no competing interests.
EDAT- 2022/09/01 06:00
MHDA- 2022/09/09 06:00
PMCR- 2022/08/31
CRDT- 2022/08/31 23:12
PHST- 2022/02/15 00:00 [received]
PHST- 2022/08/12 00:00 [accepted]
PHST- 2022/08/08 00:00 [revised]
PHST- 2022/08/31 23:12 [entrez]
PHST- 2022/09/01 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/08/31 00:00 [pmc-release]
AID - 10.1038/s41398-022-02120-8 [pii]
AID - 2120 [pii]
AID - 10.1038/s41398-022-02120-8 [doi]
PST - epublish
SO  - Transl Psychiatry. 2022 Aug 31;12(1):355. doi: 10.1038/s41398-022-02120-8.