TY - JOUR
T1 - Brain-enriched MicroRNA-184 is downregulated in older adults with major depressive disorder
T2 - A translational study
AU - Mendes-Silva, Ana Paula
AU - Fujimura, Patricia Tiemi
AU - Silva, Jéssica Regina da Costa
AU - Teixeira, Antonio Lucio
AU - Vieira, Erica Marciano
AU - Guedes, Pedro Henrique Gonçalves
AU - Barroso, Lucélia Scarabeli Silva
AU - Nicolau, Mariana de Souza
AU - Ferreira, Jéssica Diniz Rodrigues
AU - Bertola, Laiss
AU - Nicolau, Eduardo de Souza
AU - Tolentino-Araújo, Gesiane Thamire
AU - Berlezzi, Camila Moreira Silva Ferreira
AU - Rodrigues, Tamiris Sabrina
AU - Borges, Luiza Diniz Ferreira
AU - Gomes, Matheus de Souza
AU - Amaral, Laurence Rodrigues do
AU - Bonetti, Ana Maria
AU - Ueira-Vieira, Carlos
AU - Diniz, Breno Satler
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/4
Y1 - 2019/4
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 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.
AB - 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.
KW - Biomarker
KW - Drosophila melanogaster
KW - Late-life depression
KW - Major depression
KW - MicroRNAs
KW - miR-184
UR - https://www.scopus.com/pages/publications/85061307413
UR - https://www.scopus.com/pages/publications/85061307413#tab=citedBy
U2 - 10.1016/j.jpsychires.2019.01.019
DO - 10.1016/j.jpsychires.2019.01.019
M3 - Article
C2 - 30716647
AN - SCOPUS:85061307413
SN - 0022-3956
VL - 111
SP - 110
EP - 120
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -