Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment

Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the...

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Main Authors: Yi-Yung Hung, Ming-Kung Wu, Meng-Chang Tsai, Ya-Ling Huang, Hong-Yo Kang
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/7/647
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author Yi-Yung Hung
Ming-Kung Wu
Meng-Chang Tsai
Ya-Ling Huang
Hong-Yo Kang
author_facet Yi-Yung Hung
Ming-Kung Wu
Meng-Chang Tsai
Ya-Ling Huang
Hong-Yo Kang
author_sort Yi-Yung Hung
collection DOAJ
description Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.
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spelling doaj.art-0896305b98754da584ee32c598f6cb332023-08-02T03:44:42ZengMDPI AGCells2073-44092019-06-018764710.3390/cells8070647cells8070647Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant TreatmentYi-Yung Hung0Ming-Kung Wu1Meng-Chang Tsai2Ya-Ling Huang3Hong-Yo Kang4Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, TaiwanChronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.https://www.mdpi.com/2073-4409/8/7/647major depressive disordermicroRNAmiR-146amiR-155let-7eToll-like receptor 4
spellingShingle Yi-Yung Hung
Ming-Kung Wu
Meng-Chang Tsai
Ya-Ling Huang
Hong-Yo Kang
Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment
Cells
major depressive disorder
microRNA
miR-146a
miR-155
let-7e
Toll-like receptor 4
title Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment
title_full Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment
title_fullStr Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment
title_full_unstemmed Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment
title_short Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment
title_sort aberrant expression of intracellular let 7e mir 146a and mir 155 correlates with severity of depression in patients with major depressive disorder and is ameliorated after antidepressant treatment
topic major depressive disorder
microRNA
miR-146a
miR-155
let-7e
Toll-like receptor 4
url https://www.mdpi.com/2073-4409/8/7/647
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