Mendes-Silva, A.P., Fujimura, P.T., Silva, J.R.D.C., Teixeira, A.L., Vieira, E.M., Guedes, P.H.G., Barroso, L.S.S., Nicolau, M.S., Ferreira, J.D.R., Bertola, L., Nicolau, E.S., Tolentino-Araújo, G.T., Berlezzi, C.M.S.F., Rodrigues, T.S., Borges, L.D.F., Gomes, M.S., Amaral, L.R.D., Bonetti, A.M., Ueira-Vieira, C., Diniz, B.S. (2019). Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: A translational study.  J Psychiatr Res 111(): 110--120.

FBrf0241956

Research paper

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.