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  4. Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior
 
research article

Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior

Cherix, Antoine  
•
Poitry-Yamate, Carole  
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Lanz, Bernard  
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October 12, 2022
Molecular Psychiatry

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.

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Type
research article
DOI
10.1038/s41380-022-01791-5
Web of Science ID

WOS:000866309900006

Author(s)
Cherix, Antoine  
Poitry-Yamate, Carole  
Lanz, Bernard  
Zanoletti, Olivia  
Grosse, Jocelyn  
Sandi, Carmen  
Gruetter, Rolf  
Cardinaux, Jean-Rene
Date Issued

2022-10-12

Publisher

SPRINGERNATURE

Published in
Molecular Psychiatry
Subjects

Biochemistry & Molecular Biology

•

Neurosciences

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Psychiatry

•

Neurosciences & Neurology

•

anterior cingulate cortex

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open-field test

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in-vivo

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social-isolation

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imaging biomarkers

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glucose-metabolism

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insulin-resistance

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prefrontal cortex

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bipolar disorder

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mr spectroscopy

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LGC  
LIFMET  
Available on Infoscience
October 24, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/191559
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