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Savva, C.* ; Vlassakev, I.* ; Bunney, B.G.* ; Bunney, W.E.* ; Massier, L. ; Seldin, M.* ; Sassone-Corsi, P.* ; Petrus, P.* ; Sato, S.*

Resilience to chronic stress is characterized by circadian brain-liver coordination.

Biol. Psychiatry Glob. Open. Sci. 4:100385 (2024)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background: Chronic stress has a profound impact on circadian regulation of physiology. In turn, disruption of circadian rhythms increases the risk of developing both psychiatric and metabolic disorders. To explore the role of chronic stress in modulating the links between neural and metabolic rhythms, we characterized the circadian transcriptional regulation across different brain regions and the liver as well as serum metabolomics in mice exposed to chronic social defeat stress, a validated model for studying depressive-like behaviors. Methods: Male C57BL/6J mice underwent chronic social defeat stress, and subsequent social interaction screening identified distinct behavioral phenotypes associated with stress resilience and susceptibility. Stressed mice and their control littermates were sacrificed every 4 hours over the circadian cycle for comprehensive analyses of the circadian transcriptome in the hypothalamus, hippocampus, prefrontal cortex, and liver together with assessments of the circadian circulatory metabolome. Results: Our data demonstrate that stress adaptation was characterized by reprogramming of the brain as well as the hepatic circadian transcriptome. Stress resiliency was associated with an increase in cyclic transcription in the hypothalamus, hippocampus, and liver. Furthermore, cross-tissue analyses revealed that resilient mice had enhanced transcriptional coordination of circadian pathways between the brain and liver. Conversely, susceptibility to social stress resulted in a loss of cross-tissue coordination. Circadian serum metabolomic profiles corroborated the transcriptome data, highlighting that stress-resilient mice gained circadian rhythmicity of circulating metabolites, including bile acids and sphingomyelins. Conclusions: This study reveals that resilience to stress is characterized by enhanced metabolic rhythms and circadian brain-liver transcriptional coordination.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Chronic Social Stress ; Circadian Rhythms ; Gene Expression ; Metabolism ; Mouse Model For Depressive-like Behaviors ; Multitissue Omics Analysis; Social Defeat Stress; Rhythms; Identification; Hypothalamus; Hippocampus; Expression; Physiology; Platform; Atlas
ISSN (print) / ISBN 2667-1743
e-ISSN 2667-1743
Journal Biological Psychiatry Global Open Science
Quellenangaben Volume: 4, Issue: 6, Pages: , Article Number: 100385 Supplement: ,
Publisher Elsevier
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Karolinska Institutet
Novo Nordisk Foundation
Wenner-Gren foundations
Texas AM University
NARSAD Young Investigator Award from the Brain & Behavior Research Foundation