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Cherix 2022 Mol Psychiatry

From Bioblast
Publications in the MiPMap
Cherix A, Poitry-Yamate C, Lanz B, Zanoletti O, Grosse J, Sandi C, Gruetter R, Cardinaux JR (2022) Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior.

Β» Mol Psychiatry 27:4485-501. PMID: 36224260 Open Access

Cherix Antoine, Poitry-Yamate Carole, Lanz Bernard, Zanoletti Olivia, Grosse Jocelyn, Sandi Carmen, Gruetter Rolf, Cardinaux Jean-Rene (2022) Mol Psychiatry

Abstract: 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.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CH Lausanne Sandi C

Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Other 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Homogenate 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k