PMID- 33723223
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20211204
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Mar 15
TI  - Inhibition of mTOR signaling by genetic removal of p70 S6 kinase 1 increases 
      anxiety-like behavior in mice.
PG  - 165
LID - 10.1038/s41398-020-01187-5 [doi]
LID - 165
AB  - The mechanistic target of rapamycin (mTOR) is a ubiquitously expressed kinase 
      that acts through two complexes, mTORC1 and mTORC2, to regulate protein 
      homeostasis, as well as long lasting forms of synaptic and behavioral plasticity. 
      Alteration of the mTOR pathway is classically involved in neurodegenerative 
      disorders, and it has been linked to dysregulation of cognitive functions and 
      affective states. However, information concerning the specific involvement of the 
      p70 S6 kinase 1 (S6K1), a downstream target of the mTORC1 pathway, in learning 
      and memory processes and in the regulation of affective states remains scant. To 
      fill this gap, we exposed adult male mice lacking S6K1 to a battery of behavioral 
      tests aimed at measuring their learning and memory capabilities by evaluating 
      reference memory and flexibility with the Morris water maze, and associative 
      memory using the contextual fear conditioning task. We also studied their 
      anxiety-like and depression-like behaviors by, respectively, performing elevated 
      plus maze, open field, light-dark emergence tests, and sucrose preference and 
      forced swim tests. We found that deleting S6K1 leads to a robust anxious 
      phenotype concomitant with associative learning deficits; these symptoms are 
      associated with a reduction of adult neurogenesis and neuronal atrophy in the 
      hippocampus. Collectively, these results provide grounds for the understanding of 
      anxiety reports after treatments with mTOR inhibitors and will be critical for 
      developing novel compounds targeting anxiety.
FAU - Koehl, Muriel
AU  - Koehl M
AUID- ORCID: 0000-0002-7601-1422
AD  - Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Neurogenesis and 
      Pathophysiology Group, F-3300, Bordeaux, France. muriel.koehl@inserm.fr.
FAU - Ladeveze, Elodie
AU  - Ladeveze E
AD  - Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Neurogenesis and 
      Pathophysiology Group, F-3300, Bordeaux, France.
FAU - Catania, Caterina
AU  - Catania C
AD  - Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Energy Balance and Obesity 
      Group, F-3300, Bordeaux, France.
FAU - Cota, Daniela
AU  - Cota D
AUID- ORCID: 0000-0002-6909-2156
AD  - Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Energy Balance and Obesity 
      Group, F-3300, Bordeaux, France.
FAU - Abrous, Djoher Nora
AU  - Abrous DN
AUID- ORCID: 0000-0002-8589-305X
AD  - Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Neurogenesis and 
      Pathophysiology Group, F-3300, Bordeaux, France.
LA  - eng
GR  - postdoctoral fellowship/Fondation pour la Recherche Medicale (Foundation for 
      Medical Research in France)/
GR  - ANR-2010-1414/Agence Nationale de la Recherche (French National Research Agency)/
GR  - ANR-2010-1414/Agence Nationale de la Recherche (French National Research Agency)/
GR  - IRG n degrees 224757/EC | Seventh Framework Programme (EC Seventh Framework Programm)/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210315
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Anxiety/genetics
MH  - Male
MH  - Memory
MH  - Mice
MH  - *Ribosomal Protein S6 Kinases, 70-kDa
MH  - *Sirolimus
MH  - TOR Serine-Threonine Kinases
PMC - PMC7960700
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/03/17 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/03/15
CRDT- 2021/03/16 06:21
PHST- 2020/03/23 00:00 [received]
PHST- 2020/12/17 00:00 [accepted]
PHST- 2020/12/16 00:00 [revised]
PHST- 2021/03/16 06:21 [entrez]
PHST- 2021/03/17 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/03/15 00:00 [pmc-release]
AID - 10.1038/s41398-020-01187-5 [pii]
AID - 1187 [pii]
AID - 10.1038/s41398-020-01187-5 [doi]
PST - epublish
SO  - Transl Psychiatry. 2021 Mar 15;11(1):165. doi: 10.1038/s41398-020-01187-5.