TY  - JOUR
PY  - 2019//
TI  - Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder: a translational study
JO  - Journal of psychiatric research
A1  - Mendes-Silva, Ana Paula
A1  - Fujimura, Patricia Tiemi
A1  - Silva, Jéssica Regina da Costa
A1  - Teixeira, Antonio Lucio
A1  - Vieira, Erica Marciano
A1  - Guedes, Pedro Henrique Gonçalves
A1  - Barroso, Lucélia Scarabeli Silva
A1  - Nicolau, Mariana de Souza
A1  - Ferreira, Jéssica Diniz Rodrigues
A1  - Bertola, Laiss
A1  - Nicolau, Eduardo de Souza
A1  - Tolentino-Araújo, Gesiane Thamire
A1  - Berlezzi, Camila Moreira Silva Ferreira
A1  - Rodrigues, Tamiris Sabrina
A1  - Borges, Luiza Diniz Ferreira
A1  - Gomes, Matheus de Souza
A1  - Amaral, Laurence Rodrigues do
A1  - Bonetti, Ana Maria
A1  - Ueira-Vieira, Carlos
A1  - Diniz, Breno Satler
SP  - 110
EP  - 120
VL  - 111
IS  - 
N2  - 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<sub>2</sub>foldchange = -4.21, p = 1.2 × 10<sup>-03</sup>) and hsa-miR-1-3p (log<sub>2</sub>foldchange = -3.45, p = 1.3 × 10<sup>-02</sup>) 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.<br><br>Copyright © 2019 Elsevier Ltd. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 0022-3956
UR  - http://dx.doi.org/10.1016/j.jpsychires.2019.01.019
ID  - ref1
ER  -