Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: A translational study.

Autor: Mendes-Silva AP; Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil., Fujimura PT; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Silva JRDC; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Teixeira AL; Department of Psychiatry and Behavioral Sciences, University of Texas Medical Science Center at Houston, Houston, TX, USA., Vieira EM; Interdisciplinar Laboratory for Medical Investigations, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Guedes PHG; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Barroso LSS; Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil., Nicolau MS; Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil., Ferreira JDR; Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil., Bertola L; Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil., Nicolau ES; Interdisciplinar Laboratory for Medical Investigations, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Tolentino-Araújo GT; Interdisciplinar Laboratory for Medical Investigations, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Berlezzi CMSF; Interdisciplinar Laboratory for Medical Investigations, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Rodrigues TS; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Borges LDF; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Gomes MS; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil; Laboratory of Bioinformatics and Molecular Analysis (LBAM), Federal University of Uberlandia, Uberlandia, MG, Brazil., Amaral LRD; Laboratory of Bioinformatics and Molecular Analysis (LBAM), Federal University of Uberlandia, Uberlandia, MG, Brazil., Bonetti AM; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Ueira-Vieira C; Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil., Diniz BS; Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Geriatric Psychiatry Division, Center for Addiction and Mental Health, Toronto, ON, Canada. Electronic address: breno.diniz@camh.ca.
Jazyk: angličtina
Zdroj: Journal of psychiatric research [J Psychiatr Res] 2019 Apr; Vol. 111, pp. 110-120. Date of Electronic Publication: 2019 Jan 23.
DOI: 10.1016/j.jpsychires.2019.01.019
Abstrakt: Changes in microRNAs (miRNAs) expression have been described in major depressive disorder in young and middle-aged adults. However, no study has evaluated miRNA expression in older adults with major depression (or late-life depression [LLD]). Our primary aim was to evaluate the expression of miRNAs in subjects with LLD. We first evaluated the miRNA expression using next-generation sequencing (NGS) and then we validated the miRNAs found in NGS in an independent sample of LLD patients, using RT-qPCR. Drosophila melanogaster model was used to evaluate the impact of changes in miRNA expression on behavior. NGS analysis showed that hsa-miR-184 (log 2 foldchange = -4.21, p = 1.2 × 10 -03 ) and hsa-miR-1-3p (log 2 foldchange = -3.45, p = 1.3 × 10 -02 ) were significantly downregulated in LLD compared to the control group. RT-qPCR validated the downregulation of hsa-miR-184 (p < 0.001), but not for the hsa-miR-1-3p. The knockout flies of the ortholog of hsa-miR-184 showed significantly reduced locomotor activity at 21-24 d.p.e (p = 0.04) and worse memory retention at 21-24 d.p.e (24h post-stimulus, p = 0.02) compared to control flies. Our results demonstrated that subjects with LLD have significant downregulation of hsa-miR-184. Moreover, the knockout of hsa-miR-184 in flies lead to depressive-like behaviors, being more pronounce in older flies.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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