Aberrant Histone Modification of TNFAIP3, TLR4, TNIP2, MiR-146a, and MiR-155 in Major Depressive Disorder

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2023 May 6

PMID 37148522

Authors

Chu-Chiao Tseng

Shao-Cheng Wang

Yi-Chien Yang

Hung-Chun Fu

Chen-Kai Chou

Hong-Yo Kang

Yi-Yung Hung

Affiliations

Soon will be listed here.

Abstract

Activated toll-like receptor (TLR) signaling has been well investigated in major depressive disorder (MDD). We previously reported that TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 play important roles in regulating the toll-like receptor 4 (TLR4) signaling pathway and may serve as novel targets in the pathogenesis of MDD. Recently, aberrant histone modification has been implicated in several psychiatric disorders, including schizophrenia and mood disorder; the most thoroughly studied modification is histone 3 lysine 4 tri-methylation (H3K4me3). In this work, we aimed to explore H3K4me3 differences in the promotors of genes encoding the abovementioned factors in patients with MDD, and whether they were altered after antidepressant treatment. A total of 30 MDD patients and 28 healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were collected. The levels of H3K4me3 in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 were measured through chromatin immunoprecipitation (ChIP) followed by DNA methylation assay. Analysis of covariance was used to evaluate between-group differences after adjusting for age, sex, BMI, and smoking. In comparison with healthy controls, patients with MDD showed significantly lower H3K4me3 levels in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in PBMCs. These levels were not significantly altered after completion of a 4-week antidepressant treatment. To explore the association between depression severity and H3K4me3 levels, a multiple linear regression model was generated. The results revealed that levels of H3K4me3 in the TNIP2 promoters a negative correlation with the 17-item Hamilton Depression Rating Scale (HAND-17) score, whereas that of TLR4 had a positive correlation with this score. The present results suggest that decreased H3K4me3 levels in the promoters of the genes encoding TNFAIP3, TLR4, miR-146a, miR-155, and TNIP2 are involved in psychopathology of major depressive disorder.

Citing Articles

Late-onset major depressive disorder: exploring the therapeutic potential of enhancing cerebral brain-derived neurotrophic factor expression through targeted microRNA delivery.

Lai G, Malavolta M, Marcozzi S, Bigossi G, Giuliani M, Casoli T Transl Psychiatry. 2024; 14(1):352.

PMID: 39227372 PMC: 11371930. DOI: 10.1038/s41398-024-02935-7.

Plasma exosomes carrying mmu-miR-146a-5p and Notch signalling pathway-mediated synaptic activity in schizophrenia.

Wang Z, Wu T, Hu H, Alabed A, Cui G, Sun L J Psychiatry Neurosci. 2024; 49(4):E265-E281.

PMID: 39209459 PMC: 11374447. DOI: 10.1503/jpn.230118.

Genes associated with cellular senescence as diagnostic markers of major depressive disorder and their correlations with immune infiltration.

Chen J, Xie X, Lin M, Han H, Wang T, Lei Q Front Psychiatry. 2024; 15:1372386.

PMID: 38881549 PMC: 11179437. DOI: 10.3389/fpsyt.2024.1372386.

References

Sun H, Kennedy P, Nestler E . Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacology. 2012; 38(1):124-37. PMC: 3521990. DOI: 10.1038/npp.2012.73. View

Palma-Gudiel H, Cordova-Palomera A, Leza J, Fananas L . Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neurosci Biobehav Rev. 2015; 55:520-35. DOI: 10.1016/j.neubiorev.2015.05.016. View

Labonte B, Azoulay N, Yerko V, Turecki G, Brunet A . Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder. Transl Psychiatry. 2014; 4:e368. PMC: 3966043. DOI: 10.1038/tp.2014.3. View

Yehuda R, Flory J, Bierer L, Henn-Haase C, Lehrner A, Desarnaud F . Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry. 2014; 77(4):356-64. DOI: 10.1016/j.biopsych.2014.02.006. View

Peter C, Akbarian S . Balancing histone methylation activities in psychiatric disorders. Trends Mol Med. 2011; 17(7):372-9. PMC: 3134618. DOI: 10.1016/j.molmed.2011.02.003. View

Turner B . Reading signals on the nucleosome with a new nomenclature for modified histones. Nat Struct Mol Biol. 2005; 12(2):110-2. DOI: 10.1038/nsmb0205-110. View

Penner-Goeke S, Binder E . Epigenetics and depression . Dialogues Clin Neurosci. 2020; 21(4):397-405. PMC: 6952745. DOI: 10.31887/DCNS.2019.21.4/ebinder. View

Deussing J, Jakovcevski M . Histone Modifications in Major Depressive Disorder and Related Rodent Models. Adv Exp Med Biol. 2017; 978:169-183. DOI: 10.1007/978-3-319-53889-1_9. View

Collins B, Greer C, Coleman B, Sweatt J . Histone H3 lysine K4 methylation and its role in learning and memory. Epigenetics Chromatin. 2019; 12(1):7. PMC: 6322263. DOI: 10.1186/s13072-018-0251-8. View

10.

Hyun K, Jeon J, Park K, Kim J . Writing, erasing and reading histone lysine methylations. Exp Mol Med. 2017; 49(4):e324. PMC: 6130214. DOI: 10.1038/emm.2017.11. View

11.

Hung Y, Lin C, Kang H, Huang T . TNFAIP3, a negative regulator of the TLR signaling pathway, is a potential predictive biomarker of response to antidepressant treatment in major depressive disorder. Brain Behav Immun. 2016; 59:265-272. DOI: 10.1016/j.bbi.2016.09.014. View

12.

Chiang T, Hung Y, Wu M, Huang Y, Kang H . TNIP2 mediates GRβ-promoted inflammation and is associated with severity of major depressive disorder. Brain Behav Immun. 2021; 95:454-461. DOI: 10.1016/j.bbi.2021.04.021. View

13.

Hung Y, Kang H, Huang K, Huang T . Association between toll-like receptors expression and major depressive disorder. Psychiatry Res. 2014; 220(1-2):283-6. DOI: 10.1016/j.psychres.2014.07.074. View

14.

Zhao H, Wang L, Luo H, Li Q, Zuo X . TNFAIP3 downregulation mediated by histone modification contributes to T-cell dysfunction in systemic lupus erythematosus. Rheumatology (Oxford). 2017; 56(5):835-843. DOI: 10.1093/rheumatology/kew508. View

15.

Gong H, Sheng X, Xue J, Zhu D . Expression and role of TNIP2 in multiple organ dysfunction syndrome following severe trauma. Mol Med Rep. 2019; 19(4):2906-2912. DOI: 10.3892/mmr.2019.9893. View

16.

Xie H, Yang M, Zhang B, Liu M, Han S . Protective Role of TNIP2 in Myocardial Injury Induced by Acute Pancreatitis and Its Mechanism. Med Sci Monit. 2017; 23:5650-5656. PMC: 5718260. DOI: 10.12659/msm.904398. View

17.

Yan Z, Chen Y, Zhang X, Hua L, Huang L . Neuroprotective Function of TNFAIP3 Interacting Protein 2 Against Oxygen and Glucose Deprivation/Reoxygenation-Induced Injury in Hippocampal Neuronal HT22 Cells Through Regulation of the TLR4/MyD88/NF-κB Pathway. Neuropsychiatr Dis Treat. 2021; 17:2219-2227. PMC: 8275230. DOI: 10.2147/NDT.S308360. View

18.

Webb L, Ventura S, Ley S . ABIN-2, of the TPL-2 Signaling Complex, Modulates Mammalian Inflammation. Trends Immunol. 2019; 40(9):799-808. DOI: 10.1016/j.it.2019.07.001. View

19.

Xia M, Liu J, Wu X, Liu S, Li G, Han C . Histone methyltransferase Ash1l suppresses interleukin-6 production and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20. Immunity. 2013; 39(3):470-81. DOI: 10.1016/j.immuni.2013.08.016. View

20.

Andrus B, Blizinsky K, Vedell P, Dennis K, Shukla P, Schaffer D . Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models. Mol Psychiatry. 2010; 17(1):49-61. PMC: 3117129. DOI: 10.1038/mp.2010.119. View