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| Status |
Public on May 18, 2024 |
| Title |
Transthyretin orchestrates vitamin B12-induced stress resilience [II] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| Overall design |
PolyA selected mRNA sequenced for 16 brain (prefrontal cortex) samples from 10 weeks old, male mice in four groups: under naive condition or after 21 days of induced chronic variable stress and saline (control) or vitamin B12 injected afterwards.
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| 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 |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 13, 2024 |
| Last update date |
May 18, 2024 |
| Contact name |
Konstantin Riege |
| E-mail(s) |
konstantin.riege@leibniz-fli.de
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| Organization name |
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
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| Street address |
Beutenbergstraße 11
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| City |
Jena |
| ZIP/Postal code |
07745 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| GSM8264256 |
PFC_M_naive, rep4 |
| GSM8264257 |
PFC_M_CVS, rep1 |
| GSM8264258 |
PFC_M_CVS, rep2 |
| GSM8264259 |
PFC_M_CVS, rep3 |
| GSM8264260 |
PFC_M_CVS, rep4 |
| GSM8264261 |
PFC_M_naive_vB12, rep1 |
| GSM8264262 |
PFC_M_naive_vB12, rep2 |
| GSM8264263 |
PFC_M_naive_vB12, rep3 |
| GSM8264264 |
PFC_M_naive_vB12, rep4 |
| GSM8264265 |
PFC_M_CVS_vB12, rep1 |
| GSM8264266 |
PFC_M_CVS_vB12, rep2 |
| GSM8264267 |
PFC_M_CVS_vB12, rep3 |
| GSM8264268 |
PFC_M_CVS_vB12, rep4 |
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| Relations |
| BioProject |
PRJNA1111103 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE267339_pfc-vb12-counts.tsv.gz |
870.4 Kb |
(ftp)(http) |
TSV |
| GSE267339_pfc-vb12-tpm.tsv.gz |
3.6 Mb |
(ftp)(http) |
TSV |
| GSE267339_pfc-vb12-vsc.tsv.gz |
3.0 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
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