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

• Published in: Journal of psychiatric research Vol. 111; pp. 110 - 120
• Main Authors: Mendes-Silva, Ana Paula, Fujimura, Patricia Tiemi, Silva, Jéssica Regina da Costa, Teixeira, Antonio Lucio, Vieira, Erica Marciano, Guedes, Pedro Henrique Gonçalves, Barroso, Lucélia Scarabeli Silva, Nicolau, Mariana de Souza, Ferreira, Jéssica Diniz Rodrigues, Bertola, Laiss, Nicolau, Eduardo de Souza, Tolentino-Araújo, Gesiane Thamire, Berlezzi, Camila Moreira Silva Ferreira, Rodrigues, Tamiris Sabrina, Borges, Luiza Diniz Ferreira, Gomes, Matheus de Souza, Amaral, Laurence Rodrigues do, Bonetti, Ana Maria, Ueira-Vieira, Carlos, Diniz, Breno Satler
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2019
• Subjects: Biomarker; Drosophila melanogaster; Late-life depression; Major depression; MicroRNAs; miR-184; Biomarker; miR-184; Major depression; Drosophila melanogaster; Late-life depression; MicroRNAs
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2019.01.019

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 (log2foldchange = −4.21, p = 1.2 × 10−03) and hsa-miR-1-3p (log2foldchange = −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. •Late-life depression is complex and heterogeneous disorder.•Abnormalities in microRNA expression may play a role in its pathophysiology mechanism.•Next generation RNA sequencing showed a significant downregulation of mir-184 in late-life depression.•Flies with knocked-out of mir-184 showed a decreased locomotor activity and worse memory retention, more significant at older ages.•Downregulation of mir-184 may be linked to the development of depression and cognitive impairment in the elderly.