Vitamin A5/X controls stress-adaptation and prevents depressive-like behaviors in a mouse model of chronic stress.

Fiche publication

Date publication

novembre 2021

Journal

Neurobiology of stress

Auteurs

Membres identifiés du Cancéropôle Est :
Dr KREZEL Wojciech

Tous les auteurs :
Krzyżosiak A, Podleśny-Drabiniok A, Vaz B, Alvarez R, Rühl R, de Lera AR, Krężel W

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/34401411

Résumé

9--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 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 but not mice, supporting involvement of RXR signaling in anti-despair activity of these ligands. Importantly, similarly to BMS649, the 9CDHRA and its nutritional-precursor, 9--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.