Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
06 Jun 2024
06 Jun 2024
Historique:
received:
03
10
2023
accepted:
16
05
2024
revised:
13
05
2024
medline:
7
6
2024
pubmed:
7
6
2024
entrez:
6
6
2024
Statut:
aheadofprint
Résumé
Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action. Intersection of DEG sets against neuropsychiatric GWAS loci, sex-specific transcriptomic portraits of major depressive disorder (MDD), and mouse models of stress and depression reveals significant similarities and differences across treatments. Interestingly, molecular responses in the infralimbic cortex, basolateral amygdala and locus coeruleus are region-specific and highly similar across treatments, whilst responses in the Raphe, medial preoptic area, cingulate cortex, prelimbic cortex and ventral dentate gyrus are predominantly treatment-specific. Mechanistically, ADs concordantly downregulate immune pathways in the amygdala and ventral dentate gyrus. In contrast, protein synthesis, metabolism and synaptic signaling pathways are axes of variability among treatments. We use spatial transcriptomics to further delineate layer-specific molecular pathways and DEGs within the prefrontal cortex. Our study reveals complex AD and probiotics action on the mammalian brain and identifies treatment-specific cellular processes and gene targets associated with mood disorders.
Identifiants
pubmed: 38844534
doi: 10.1038/s41380-024-02619-0
pii: 10.1038/s41380-024-02619-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Agency for Science, Technology and Research (A*STAR)
ID : H18/01/A0/020
Organisme : Hope for Depression Research Foundation (Depression Research Foundation)
ID : 840013
Organisme : Hope for Depression Research Foundation (Depression Research Foundation)
ID : 840013
Organisme : Hope for Depression Research Foundation (Depression Research Foundation)
ID : HDRF, Ref.no. 840013
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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