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Series GSE267047 Query DataSets for GSE267047
Status Public on May 13, 2024
Title Transthyretin orchestrates vitamin B12-induced stress resilience
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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 determined vitamin B12-induced transcriptional changes related to stress resilience. By viral-mediated gene transfer and in vivo epigenome editing, we reveal a functional pathway linking vitamin B12, DNA methylation, and depressive-like symptoms. Results: We identified Transthyretin (Ttr) as a sex-specific key target of vitamin B12 action in chronic stress. Accordingly, TTR expression was increased postmortem in the prefrontal cortex of male, but not female, depressed patients. 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 establish a direct causal link between DNAme on Ttr and stress-associated behaviors. Discussion: In summary, using state-of-the-art techniques, this study uncovers a mechanistic link between cobalamin supplementation, Ttr, and markers of chronic stress and depression, encouraging further studies into dietary interventions for mood disorders.
Overall design Total mRNA sequenced for 12 brain (prefrontal cortex) samples from 14 weeks old, male mice, 4 weeks after stereotaxic surgery to infect PFC by 1) empty Adeno-associated virus constructs (GFP control), 2) AAVs to overexpress (OE) Ttr, 3) AAVs or knockdown (KD) Ttr.
Contributor(s) Stein G, Aly JS, Manzolillo A, Lange L, Riege K, Hussain I, Heller EA, Cubillos S, Ernst T, Hübner CA, Turecki G, Hoffmann S, Engmann O
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Submission date May 08, 2024
Last update date May 13, 2024
Contact name Konstantin Riege
Organization name Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Street address Beutenbergstraße 11
City Jena
ZIP/Postal code 07745
Country Germany
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM8258939 PFC_ctrl, rep1
GSM8258940 PFC_ctrl, rep2
GSM8258941 PFC_ctrl, rep3
BioProject PRJNA1109405

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE267047_pfc-ttr-counts.tsv.gz 748.1 Kb (ftp)(http) TSV
GSE267047_pfc-ttr-tpm.tsv.gz 2.9 Mb (ftp)(http) TSV
GSE267047_pfc-ttr-vsc.tsv.gz 2.4 Mb (ftp)(http) TSV
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Raw data are available in SRA

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