Transthyretin Orchestrates Vitamin B12-Induced Stress Resilience.

Autor: Stein G; Institute for Biochemistry and Biophysics, Friedrich Schiller University, Jena, Germany., Aly JS; Institute of Human Genetics, Jena University Hospital, Jena, Germany., Manzolillo A; Institute of Human Genetics, Jena University Hospital, Jena, Germany., Lange L; Institute for Biochemistry and Biophysics, Friedrich Schiller University, Jena, Germany., Riege K; Computational Biology Group, Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany., Hussain I; Institute for Biochemistry and Biophysics, Friedrich Schiller University, Jena, Germany., Heller EA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania., Cubillos S; Institute for Biochemistry and Biophysics, Friedrich Schiller University, Jena, Germany., Ernst T; Clinic for Internal Medicine II, Jena University Hospital, Jena, Germany., Hübner CA; Institute of Human Genetics, Jena University Hospital, Jena, Germany., Turecki G; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Québec, Canada., Hoffmann S; Computational Biology Group, Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany., Engmann O; Institute for Biochemistry and Biophysics, Friedrich Schiller University, Jena, Germany; Institute of Human Genetics, Jena University Hospital, Jena, Germany. Electronic address: olivia.engmann@uni-jena.de.
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2024 Jul 17. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1016/j.biopsych.2024.07.009
Abstrakt: Background: Chronic stress significantly contributes to mood and anxiety disorders. Previous data suggest a correlative connection between vitamin B12 supplementation, depression, and stress resilience. However, the underlying mechanisms are still poorly understood.
Methods: Using the chronic variable stress mouse model coupled with RNA sequencing, we identified vitamin B12-induced transcriptional changes related to stress resilience. Using viral-mediated gene transfer and in vivo epigenome editing, we revealed a functional pathway linking vitamin B12, DNA methylation (DNAme), and depression-like symptoms.
Results: We identified Ttr (transthyretin) as a key sex-specific target of vitamin B12 in chronic stress. Accordingly, TTR expression was increased postmortem in the prefrontal cortex of male but not female patients with depression. Virally altered Ttr in the prefrontal cortex functionally contributed to stress- and depression-related behaviors, changes in dendritic spine morphology, and gene expression. In stressed mice, vitamin B12 reduced DNAme in the Ttr promoter region. Importantly, using in vivo epigenome editing to alter DNAme in the brains of living mice for the first time, we established a direct causal link between DNAme and Ttr and stress-associated behaviors.
Conclusions: Using state-of-the-art techniques, this study uncovered a mechanistic link between vitamin B12 supplementation, Ttr, and markers of chronic stress and depression, encouraging further studies into dietary interventions for mood disorders.
(Copyright © 2024 Society of Biological Psychiatry. All rights reserved.)
Databáze: MEDLINE
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