Histone acetylation and expression of mono-aminergic transmitters synthetases involved in CUS-induced depressive rats
Abstract
Histone acetylation has been linked to depression, the etiology of which involves many factors such as genetics, environments, and epigenetics. The aim of the present study was to investigate whether it was associated with epigenetic histone modification and gene expression of enzymes responsible for the biosynthesis of norepinephrine and serotonin in rat depression model induced by chronic unpredictable stress (CUS). Eight-week-old male Sprague-Dawley rats were exposed to CUS over 28 days. It was shown that the CUS-induced rats displayed remarked anxiety- and depression-like behavior with weakened locomotor activity in open field test and prolonged immobility in forced swimming test. Western blot revealed that CUS led to significant decrease in acetylation of H3 at Lysine 9 (K9) and H4 at Lysine 12 (K12) with obviously increasing histone deacetylases 5 (HDAC5) expression in hippocampus of CUS-induced rats. Meanwhile, there was an obviously decreased expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) both at protein and mRNA levels. Administration of sodium valproate (VPA), a histone deacetylase 5 (HDAC5) inhibitor, not only significantly relieved the anxiety- and depression-like behaviors of CUS-induced rats but also clearly blunted decrease of H3(K9) and H4(K12) acetylation and expression of TH and TPH, and prevented increase of HDAC5 expression. The results indicate that there exists possible interrelation between TH and TPH gene expression and epigenetic histone acetylation in CUS-induced depressive rats, which at least partly contributes to the etiology of depression.
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These molecular alterations indicate disrupted monoaminergic signaling, a core neurobiological feature of depression.
“These molecular alterations indicate disrupted monoaminergic signaling, a core neurobiological feature of depression (Liu et al., 2014).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Liu et al., 2014
In chronic unpredictable stress models, acetylation at H3K9ac and H4K12ac sites is markedly reduced in the hippocampus and prefrontal cortex, accompanied by increased expression of HDAC5.
“In chronic unpredictable stress (CUS) models, acetylation at H3K9ac and H4K12ac sites is markedly reduced in the hippocampus and prefrontal cortex, accompanied by increased expression of histone deacetylase 5 (HDAC5).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Liu et al., 2014
This hypoacetylation is associated with reduced tyrosine hydroxylase expression in the locus coeruleus and decreased tryptophan hydroxylase activity in the hippocampus.
“This hypoacetylation is associated with reduced tyrosine hydroxylase (TH) expression in the locus coeruleus and decreased tryptophan hydroxylase (TPH) activity in the hippocampus—two enzymes essential for dopamine and serotonin synthesis, respectively.”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Liu et al., 2014
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- Authors
- Liu, D., Qiu, H.-M., Fei, H.-Z., Hu, X.-Y., Xia, H.-J., Wang, L.-J., Qin, L.-J., Jiang, X.-H., & Zhou, Q.-X.
- Affiliations
- Chongqing Medical University (CN)
- Department of Pharmacology, School of Pharmacy of Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016
- Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing 400042, China
- Corresponding author
- Zhou, Qi-Xin
- ORCID
- Venue
- Experimental Biology and Medicine
- Publisher
- Frontiers Media SA
- Published
- 2014-02-04
- Volume
- 239
- Issue
- 3
- Pages
- 330-336
- ISSN
- 0071-3384 (ISSN-L)
- 1535-3702
- 1535-3699
- OpenAlex
- W2001552899
- Cited by
- 49
- References
- 38
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 9 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 2
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- histone acetylation, chronic unpredictable mild stress, depression, HDAC5, tyrosine hydroxylase, tryptophan hydroxylase, norepinephrine synthesis, serotonin synthesis, valproic acid, hippocampus, anxiety-like behavior, locomotor activity, forced swim test
- MeSH terms
- Acetylation, Animals, Anxiety, Depression, Disease Models, Animal, Hippocampus, Histone Deacetylases, Histones, Male, Norepinephrine, RNA, Messenger, Serotonin, Stress, Psychological, Tryptophan Hydroxylase, Tyrosine 3-Monooxygenase, Valproic Acid, Gene Expression, Rats, Sprague-Dawley, Epigenesis, Genetic, Rats, Histone Deacetylase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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