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

Ana Paula Mendes-Silva, Patricia Tiemi Fujimura, Jéssica Regina da Costa Silva, Antonio Lucio Teixeira, Erica Marciano Vieira, Pedro Henrique Gonçalves Guedes, Lucélia Scarabeli Silva Barroso, Mariana de Souza Nicolau, Jéssica Diniz Rodrigues Ferreira, Laiss Bertola, Eduardo de Souza Nicolau, Gesiane Thamire Tolentino-Araújo, Camila Moreira Silva Ferreira Berlezzi, Tamiris Sabrina Rodrigues, Luiza Diniz Ferreira Borges, Matheus de Souza Gomes, Laurence Rodrigues do Amaral, Ana Maria Bonetti, Carlos Ueira-Vieira, Breno Satler Diniz

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)110-120
Number of pages11
JournalJournal of Psychiatric Research
Volume111
DOIs
StatePublished - Apr 2019
Externally publishedYes

Keywords

  • Biomarker
  • Drosophila melanogaster
  • Late-life depression
  • Major depression
  • MicroRNAs
  • miR-184

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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