Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function.
Animals
Gastrointestinal Microbiome
/ drug effects
Mitochondria
/ metabolism
Corticosterone
Mice
Depression
Ceramides
/ metabolism
Dysbiosis
Hippocampus
/ metabolism
Fecal Microbiota Transplantation
Male
Disease Models, Animal
Feces
/ microbiology
Mice, Inbred C57BL
Neurogenesis
Behavior, Animal
/ drug effects
Journal
NPJ biofilms and microbiomes
ISSN: 2055-5008
Titre abrégé: NPJ Biofilms Microbiomes
Pays: United States
ID NLM: 101666944
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
16
10
2023
accepted:
10
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
The role of gut microbiota (GM) dysbiosis in the pathogenesis of depression has received widespread attention, but the mechanism remains elusive. Corticosterone (CORT)-treated mice showed depression-like behaviors, reduced hippocampal neurogenesis, and altered composition of the GM. Fecal microbial transplantation from CORT-treated mice transferred depression-like phenotypes and their dominant GM to the recipients. Fecal metabolic profiling exposed remarkable increase of gut ceramides in CORT-treated and recipient mice. Oral gavage with Bifidobacterium pseudolongum and Lactobacillus reuteri could induce elevations of gut ceramides in mice. Ceramides-treated mice showed depressive-like phenotypes, significant downregulation of oxidative phosphorylation-associated genes, and hippocampal mitochondrial dysfunction. Our study demonstrated a link between chronic exposure to CORT and its impact on GM composition, which induces ceramides accumulation, ultimately leading to hippocampal mitochondrial dysfunction. This cascade of events plays a critical role in reducing adult hippocampal neurogenesis and is strongly associated with the development of depression-like behaviors.
Identifiants
pubmed: 39468065
doi: 10.1038/s41522-024-00582-w
pii: 10.1038/s41522-024-00582-w
doi:
Substances chimiques
Corticosterone
W980KJ009P
Ceramides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82371176
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81801331
Informations de copyright
© 2024. The Author(s).
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