Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_AF63783C3E28
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior.
Périodique
Molecular psychiatry
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Statut éditorial
Publié
Date de publication
11/2022
Peer-reviewed
Oui
Volume
27
Numéro
11
Pages
4485-4501
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Mood disorders (MD) are a major burden on society as their biology remains poorly understood, challenging both diagnosis and therapy. Among many observed biological dysfunctions, homeostatic dysregulation, such as metabolic syndrome (MeS), shows considerable comorbidity with MD. Recently, CREB-regulated transcription coactivator 1 (CRTC1), a regulator of brain metabolism, was proposed as a promising factor to understand this relationship. Searching for imaging biomarkers and associating them with pathophysiological mechanisms using preclinical models can provide significant insight into these complex psychiatric diseases and help the development of personalized healthcare. Here, we used neuroimaging technologies to show that deletion of Crtc1 in mice leads to an imaging fingerprint of hippocampal metabolic impairment related to depressive-like behavior. By identifying a deficiency in hippocampal glucose metabolism as the underlying molecular/physiological origin of the markers, we could assign an energy-boosting mood-stabilizing treatment, ebselen, which rescued behavior and neuroimaging markers. Finally, our results point toward the GABAergic system as a potential therapeutic target for behavioral dysfunctions related to metabolic disorders. This study provides new insights on Crtc1's and MeS's relationship to MD and establishes depression-related markers with clinical potential.
Mots-clé
Mice, Animals, Transcription Factors/genetics, Transcription Factors/metabolism, Hippocampus/metabolism, Behavior, Animal/physiology, Depression/genetics, Depression/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/10/2022 14:15
Dernière modification de la notice
28/12/2022 7:52