Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil.
Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, Brazil.
J Psychiatr Res. 2019 Apr;111:110-120. doi: 10.1016/j.jpsychires.2019.01.019. Epub 2019 Jan 23.
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 (logfoldchange = -4.21, p = 1.2 × 10) and hsa-miR-1-3p (logfoldchange = -3.45, p = 1.3 × 10) 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.
miRNAs（微小 RNA）表达的变化已在年轻和中年成年人的重度抑郁症中被描述。然而，没有研究评估过患有重度抑郁症（或老年抑郁症 [LLD]）的老年人的 miRNA 表达。我们的主要目的是评估 LLD 患者的 miRNA 表达。我们首先使用下一代测序（NGS）评估 miRNA 表达，然后在独立的 LLD 患者样本中使用 RT-qPCR 验证 NGS 中发现的 miRNA。使用黑腹果蝇模型来评估 miRNA 表达变化对行为的影响。NGS 分析显示，与对照组相比，LLD 中 hsa-miR-184（logfoldchange = -4.21，p = 1.2×10）和 hsa-miR-1-3p（logfoldchange = -3.45，p = 1.3×10）的表达显著下调。RT-qPCR 验证了 hsa-miR-184 的下调（p<0.001），但 hsa-miR-1-3p 没有。hsa-miR-184 的同源物敲除果蝇在 21-24 d.p.e 时表现出明显减少的运动活性（p=0.04），并且在 21-24 d.p.e 时（刺激后 24 小时，p=0.02）记忆保留更差。我们的结果表明，LLD 患者 hsa-miR-184 表达显著下调。此外，果蝇中 hsa-miR-184 的敲除导致抑郁样行为，在较老的果蝇中更为明显。
