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.
Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: A translational study / 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. D. S.; Ferreira, J. D. R.; Bertola, L.; Nicolau, E. D. S.; Tolentino-Araujo, G. T.; Berlezzi, C. M. S. F.; Rodrigues, T. S.; Borges, L. D. F.; Gomes, M. D. S.; Amaral, L. R. D.; Bonetti, A. M.; Ueira-Vieira, C.; Diniz, B. S.. - In: JOURNAL OF PSYCHIATRIC RESEARCH. - ISSN 0022-3956. - 111:(2019), pp. 110-120. [10.1016/j.jpsychires.2019.01.019]
Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: A translational study
Borges L. D. F.;
2019
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 (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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.