PMID- 34401411
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210818
IS  - 2352-2895 (Print)
IS  - 2352-2895 (Electronic)
IS  - 2352-2895 (Linking)
VI  - 15
DP  - 2021 Nov
TI  - Vitamin A5/X controls stress-adaptation and prevents depressive-like behaviors in 
      a mouse model of chronic stress.
PG  - 100375
LID - 10.1016/j.ynstr.2021.100375 [doi]
LID - 100375
AB  - 9-cis-13,14-dihydroretinoic acid (9CDHRA), acts as an endogenous ligand of the 
      retinoid X receptors (RXRs), and is an active form of a suggested new vitamin, 
      vitamin A5/X. Nutritional-relevance of this pathway as well as its detailed role 
      in vertebrate physiology, remain largely unknown. Since recent GWAS data and 
      experimental studies associated RXR-mediated signaling with depression, we 
      explored here the relevance of RXR and vitamin A5/X-mediated signaling in the 
      control of stress adaptation and depressive-like behaviors in mice. We found that 
      compromised availability of 9CDHRA in Rbp1-/- mice was associated with increased 
      despair in the forced swim and anhedonia in the sucrose preference test. 9CDHRA 
      similarly to synthetic RXR agonist, BMS649, normalized despair behaviors in 
      Rbp1-/- but not Rxrgamma-/- mice, supporting involvement of RXR signaling in 
      anti-despair activity of these ligands. Importantly, similarly to BMS649, the 
      9CDHRA and its nutritional-precursor, 9-cis-13,14-dihydroretinol (vitamin A5/X 
      alcohol), prevented development of depressive-like behaviors in mice exposed to 
      chronic social defeat stress, revealing the beneficial role of RXRs and its 
      endogenous ligand in stress adaptation process. These data point to the need for 
      relevant nutritional, biochemical and pharmacological studies of this signaling 
      pathway in human, both in physiological conditions and in pathologies of 
      stress-related disorders.
CI  - (c) 2021 Published by Elsevier Inc.
FAU - Krzyzosiak, Agnieszka
AU  - Krzyzosiak A
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Inserm, 
      U-964, CNRS UMR-7104, Universite de Strasbourg, Illkirch, France.
FAU - Podlesny-Drabiniok, Anna
AU  - Podlesny-Drabiniok A
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Inserm, 
      U-964, CNRS UMR-7104, Universite de Strasbourg, Illkirch, France.
FAU - Vaz, Belen
AU  - Vaz B
AD  - Departamento de Quimica Organica, Universidade de Vigo, Facultad de Quimica, 
      Vigo, Spain.
FAU - Alvarez, Rosana
AU  - Alvarez R
AD  - Departamento de Quimica Organica, Universidade de Vigo, Facultad de Quimica, 
      Vigo, Spain.
FAU - Ruhl, Ralph
AU  - Ruhl R
AD  - CISCAREX UG, Berlin, Germany.
AD  - Paprika-Bioanalytics BT, Debrecen, Hungary.
FAU - de Lera, Angel R
AU  - de Lera AR
AD  - Departamento de Quimica Organica, Universidade de Vigo, Facultad de Quimica, 
      Vigo, Spain.
FAU - Krezel, Wojciech
AU  - Krezel W
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Inserm, 
      U-964, CNRS UMR-7104, Universite de Strasbourg, Illkirch, France.
LA  - eng
PT  - Journal Article
DEP - 20210803
PL  - United States
TA  - Neurobiol Stress
JT  - Neurobiology of stress
JID - 101643409
PMC - PMC8355947
OTO - NOTNLM
OT  - Chronic stress
OT  - Depression
OT  - Mouse models
OT  - Retinoid receptors
OT  - Vitamin A
COIS- A.K., A.P.-D., B.V., R.A. report no conflict of interests. W.K., A.R.d.L. and 
      R.R. are inventors of the patent family "Precursor compounds for providing 
      retinoids of the vitamin A5 pathway and uses thereof" PCT/HU 2017/091937, 
      US16102137, 127356JP-18340, 127578AU-18340, 127579CN-18340, 128446CA-18340. W.K., 
      A.R.d.L. and R.R. are shareholders of CISCAREX UG.
EDAT- 2021/08/18 06:00
MHDA- 2021/08/18 06:01
PMCR- 2021/08/03
CRDT- 2021/08/17 07:32
PHST- 2021/05/12 00:00 [received]
PHST- 2021/07/26 00:00 [revised]
PHST- 2021/07/30 00:00 [accepted]
PHST- 2021/08/17 07:32 [entrez]
PHST- 2021/08/18 06:00 [pubmed]
PHST- 2021/08/18 06:01 [medline]
PHST- 2021/08/03 00:00 [pmc-release]
AID - S2352-2895(21)00083-7 [pii]
AID - 100375 [pii]
AID - 10.1016/j.ynstr.2021.100375 [doi]
PST - epublish
SO  - Neurobiol Stress. 2021 Aug 3;15:100375. doi: 10.1016/j.ynstr.2021.100375. 
      eCollection 2021 Nov.