Cited by 49Stress Responses and CortisolHistone Deacetylase Inhibitors ResearchTreatment of Major Depression

Histone acetylation and expression of mono-aminergic transmitters synthetases involved in CUS-induced depressive rats

Liu, Dan, Qiu, Hong-Mei, Fei, Hui-Zhi, Hu, Xiao-Ya, Xia, Hai-Jian, Wang, Li-Jia, Qin, Li-Juan, Jiang, Xin-Hui +1 more·2014·Experimental Biology and Medicine

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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Crossref · 10.1177/1535370213513987

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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).”
  • 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).”
  • 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.”

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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
Venue
Experimental Biology and Medicine
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

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