Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors
Abstract
Major depressive disorder (MDD) is one of the most debilitating and severe mental diseases globally. Increasing evidence has shown that epigenetics is critical for understanding brain function and brain disorders, including MDD. N-acetyltransferase 10 (NAT10), acting on histones, mRNA and other substrates, has been reported to be involved in epigenetic events, including histone acetylation and mRNA modifications. NAT10 is highly expressed in the brain. However, the potential effects of NAT10 on MDD are still unknown. Here, we exploited chronic mild stress (CMS) to induce anxiety- and depression-like behaviors in mice and found that the expression of NAT10 in the mouse hippocampus was upregulated after CMS treatment. Inhibition of NAT10 by pharmacological methods produced anxiolytic- and antidepressant-like effects. Neuron-specific overexpression of NAT10 in the hippocampus resulted in anxiety- and depression-like behaviors, accompanied by higher SIRT1 protein levels, and lower dendritic spine densities. Overall, it was found that elevation of NAT10 in hippocampal neurons is involved in the occurrence of anxiety- and depression-like behaviors, suggesting that NAT10 could be a potential new target for developing anxiolytics and antidepressants.
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Pharmacological methods prevented NAT10's anti-anxiety and antidepressant-like effects.
“Pharmacological methods prevented NAT10’s anti-anxiety and antidepressant-like effects.369”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [369]
In mice, chronic mild stress triggers anxiety and depression-like behavior, and results indicated an increase in NAT10 expression in the hippocampus following CMS.
“In a study conducted on mice, chronic mild stress (CMS) was used to trigger anxiety and depression-like behavior, and the results indicated an increase in NAT10 expression in the hippocampus following the administration of CMS.”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [369]
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“369 As one of the most abundant modi fi cations on tRNA and rRNA, m5C is enzymatically catalyzed by members of the NOL1/NOP2/SUN domain (NSUN) family and DNA methyltransferase homolog DNMT2.”
Background
- Authors
- Guo, X.-F., Wang, X.-H., Fu, Y.-L., Meng, Q., Huang, B.-Y., Yang, R., Guo, Y., Du, Y.-R., Wang, X., Gao, Y., Song, L., Gong, M., Wang, S., Li, Y.-D., Shi, H.-S., & Shi, Y.
- Affiliations
- Hebei Medical University (CN)
- Corresponding author
- Shi, Yun
- Venue
- Brain Research Bulletin
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 185
- Pages
- 91-98
- ISSN
- 0361-9230 (ISSN-L)
- OpenAlex
- W4229442806
- Semantic Scholar
- e5850355cb28db6aff95bcb4ffaafd062eb1329e
- Cited by
- 32
- References
- 34
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 5 · 2023: 8
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Research Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82171536, 81800742)
- Natural Science Foundation of Hebei Province (H2020206481, A201802022, H2021206203, SLRC2019047, H2018206119)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- NAT10, major depressive disorder, anxiety-like behavior, depression-like behavior, hippocampal neurons, chronic mild stress, histone acetylation, SIRT1, dendritic spine density, epigenetics, antidepressant targets, anxiolytic effects
- MeSH terms
- Acetyltransferases, Animals, Antidepressive Agents, Anxiety, Depression, Depressive Disorder, Major, Major Depressive Disorder, Hippocampus, Neurons, RNA, Messenger, Stress, Psychological, Mice
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