Physical Exercise Prevented Stress‐Induced Anxiety via Improving Brain RNA Methylation
Open accessAbstract
Physical exercise is effective in alleviating mental disorders by improving synaptic transmission; however, the link between body endurance training and neural adaptation has not yet been completely resolved. In this study, the authors investigated the role of RNA N 6‐methyladenosine (m6A), an emerging epigenetic mechanism, in improved resilience against chronic restraint stress. A combination of molecular, behavioral, and in vivo recording data demonstrates exercise‐mediated restoration of m6A in the mouse medial prefrontal cortex, whose activity is potentiated to exert anxiolytic effects. Furthermore, it is revealed that hepatic biosynthesis of one methyl donor is necessary for exercise to improve brain RNA m6A to counteract environmental stress. This novel liver‐brain axis provides an explanation for brain network changes upon exercise training and provides new insights into the diagnosis and treatment of anxiety disorders.
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Physical exercise alleviates anxiety-like behaviors and restores m6A levels in mouse medial prefrontal cortex.
“One study found that physical exercise alleviates anxiety-like behaviors and restores m6A levels in mouse medial prefrontal cortex; the restoration of m6A is related to increased expression of RNA Methylase (i.e., METTL3, METTL14, METTL16) and downregulation of RNA demethylase (i.e., ALKBH5), as well as upregulated expression of the RNA-binding factor YTHDF3.374”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [374]
Restoration of m6A after physical exercise is related to increased expression of METTL3, METTL14, METTL16 and downregulation of ALKBH5, as well as upregulated YTHDF3.
“the restoration of m6A is related to increased expression of RNA Methylase (i.e., METTL3, METTL14, METTL16) and downregulation of RNA demethylase (i.e., ALKBH5), as well as upregulated expression of the RNA-binding factor YTHDF3.374”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [374]
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“, ALKBH5), as well as upregulated expression of the RNA-binding factor YTHDF3.(374) 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.”
Background
- Authors
- Yan, L., Wei, J., Yang, F., Wang, M., Wang, S., Cheng, T., Liu, X., Jia, Y., So, K., & Zhang, L.
- Affiliations
- Jinan University (CN)
- Corresponding author
- Jia, Yanbin
- So, Kwok‐Fai
- Zhang, Li
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2022-06
- Volume
- 9
- Issue
- 24
- Pages
- e2105731-e2105731
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC9404392
- OpenAlex
- W4281617200
- Cited by
- 83
- References
- 66
- Citations by year
- 2026: 20 · 2025: 26 · 2024: 25 · 2023: 10 · 2022: 2
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (32070955, 81771455, 81971067)
- National Key Research and Development Program of China (2020YFA0113600)
- Natural Science Foundation of Guangdong Province (2019A1515011772)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- physical activity, anxiety, chronic restraint stress, RNA N6-methyladenosine, m6A RNA methylation, epigenetics, medial prefrontal cortex, methyl donors, liver-brain axis, exercise training, stress resilience, anxiety disorders
- MeSH terms
- Animals, Anxiety, Anxiety Disorders, Brain, Humans, Methylation, RNA, Mice
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