1. Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: A translational study.
- Author
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Mendes-Silva AP, Fujimura PT, Silva JRDC, Teixeira AL, Vieira EM, Guedes PHG, Barroso LSS, Nicolau MS, Ferreira JDR, Bertola L, Nicolau ES, Tolentino-Araújo GT, Berlezzi CMSF, Rodrigues TS, Borges LDF, Gomes MS, Amaral LRD, Bonetti AM, Ueira-Vieira C, and Diniz BS
- Subjects
- Age Factors, Aged, Animals, Animals, Genetically Modified, Disease Models, Animal, Down-Regulation, Drosophila Proteins, Drosophila melanogaster, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Sequence Analysis, RNA, Translational Research, Biomedical, Aging genetics, Behavior, Animal, Cognitive Dysfunction genetics, Depressive Disorder, Major genetics, Locomotion genetics, MicroRNAs genetics, Retention, Psychology
- Abstract
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 (log2 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.)- Published
- 2019
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