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
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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Auteurs

Nirmala Arul Rayan (NA)

Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, 138672, Singapore.

Jonathan Aow (J)

Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, 138672, Singapore.
NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Michelle Gek Liang Lim (MGL)

Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, 138672, Singapore.

Danusa Mar Arcego (DM)

Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada.

Richard Ryan (R)

Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada.

Nooshin Nourbakhsh (N)

Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, 138672, Singapore.

Randriely Merscher Sobreira de Lima (RMS)

Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada.

Kelly Craig (K)

Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada.

Tie Yuan Zhang (TY)

Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada.

Yeek Teck Goh (YT)

Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, 138672, Singapore.

Alfred Xuyang Sun (AX)

Duke-NUS Graduate Medical School, Signature Research Program in Neuroscience and Behavioural Disorders, 8 College Road, Singapore, 169857, Singapore.

Thomas Tompkins (T)

Lallemand Bio-Ingredients, 1620 Rue Prefontaine, Montréal, QC, H1W 2N8, Canada.

Stéphane Bronner (S)

Lallemand Health Solutions, Rosell Institute for Microbiome and Probiotics, 6100 Avenue Royalmount, Montréal, QC, H4P 2R2, Canada.

Sylvie Binda (S)

Lallemand Health Solutions, Rosell Institute for Microbiome and Probiotics, 6100 Avenue Royalmount, Montréal, QC, H4P 2R2, Canada.

Josie Diorio (J)

Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada.

Carine Parent (C)

Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada.

Michael J Meaney (MJ)

NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. michael.meaney@mcgill.ca.
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, QC, H4H 1R3, Canada. michael.meaney@mcgill.ca.
Singapore Institute for Clinical Sciences, A*STAR, Singapore, 117609, Singapore. michael.meaney@mcgill.ca.
Brain-Body Initiative, Institute for Cell & Molecular Biology, A*STAR, Singapore, Singapore. michael.meaney@mcgill.ca.

Shyam Prabhakar (S)

Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, 138672, Singapore. prabhakars@gis.a-star.edu.sg.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore. prabhakars@gis.a-star.edu.sg.
Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. prabhakars@gis.a-star.edu.sg.

Classifications MeSH