Epitranscriptome of the ventral tegmental area in a deep brain-stimulated chronic unpredictable mild stress mouse model
Open accessAbstract
Deep brain stimulation (DBS) applied to the nucleus accumbens (NAc) alleviates the depressive symptoms of major depressive disorders. We investigated the mechanism of this effect by assessing gene expression and RNA methylation changes in the ventral tegmental area (VTA) following NAc-DBS in a chronic unpredictable mild stress (CUMS) mouse model of depression. Gene expression and N 6-methyladenosine (m 6 A) levels in the VTA were measured in mice subjected to CUMS and then DBS, and transcriptome-wide m 6 A changes were profiled using immunoprecipitated methylated RNAs with microarrays, prior to gene ontology analysis. The expression levels of genes linked to neurotransmitter receptors, transporters, transcription factors, neuronal activities, synaptic functions, and mitogen-activated protein kinase and dopamine signaling were upregulated in the VTA upon NAc-DBS. Furthermore, m 6 A modifications included both hypermethylation and hypomethylation, and changes were positively correlated with the upregulation of some genes. Moreover, the effects of CUMS on gene expression and m 6 A-mRNA modification were reversed by DBS for some genes. Interestingly, while the expression of certain genes was not changed by DBS, long-term stimulation did alter their m 6 A modifications. NAc-DBS-induced modifications are correlated largely with upregulation but sometimes downregulation of genes in CUMS mice. Our findings improve the current understanding of the molecular mechanisms underlying DBS effects on depression.
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“Another study showed that NAc-deep brain stimulation (DBS) could reverse the impacts of CUMS on gene expression and m(6)A-mRNA modification for certain genes, but the m(6)A-regulating enzymes were not detected.(375) CHROMATIN REMODELING FACTOR ALTERATION IS ASSOCIATED WITH MDD Modifying chromatin structure by ATP-depe…”
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- Authors
- Song, N., Du, J., Gao, Y., & Yang, S.
- Affiliations
- Academy of Military Medical Sciences (CN)
- Corresponding author
- Song, Nan
- Venue
- Translational Neuroscience
- Publisher
- Walter de Gruyter GmbH
- Published
- 2020-01-01
- Volume
- 11
- Issue
- 1
- Pages
- 402-418
- ISSN
- 2081-3856 (ISSN-L)
- 2081-6936
- PMC
- PMC7724003
- OpenAlex
- W3098358315
- Cited by
- 15
- References
- 70
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 3
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- China Postdoctoral Science Foundation
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- deep brain stimulation, nucleus accumbens, ventral tegmental area, chronic unpredictable mild stress, depression, N6-methyladenosine, RNA methylation, epitranscriptome, gene expression, dopamine signaling, mitogen-activated protein kinase, neurotransmitter receptors, synaptic function
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