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 (log2foldchangeâ¯=â¯-4.21, pâ¯=â¯1.2â¯×â¯10-03) and hsa-miR-1-3p (log2foldchangeâ¯=â¯-3.45, pâ¯=â¯1.3â¯×â¯10-02) were significantly downregulated in LLD compared to the control group. RT-qPCR validated the downregulation of hsa-miR-184 (pâ¯<â¯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 21-24â¯d.p.e (pâ¯=â¯0.04) and worse memory retention at 21-24â¯d.p.e (24h post-stimulus, pâ¯=â¯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.
Subject(s)
Aging/genetics , Behavior, Animal , Cognitive Dysfunction/genetics , Depressive Disorder, Major/genetics , Locomotion , MicroRNAs/genetics , Retention, Psychology , Age Factors , Aged , Animals , Animals, Genetically Modified , Disease Models, Animal , Down-Regulation , Drosophila Proteins , Drosophila melanogaster , Female , High-Throughput Nucleotide Sequencing , Humans , Locomotion/genetics , Male , Middle Aged , Sequence Analysis, RNA , Translational Research, BiomedicalABSTRACT
Epidermal growth factor (EGF) and Fibroblast Growth Factor-2 (FGF-2) are growth factors involved neuronal growth and synaptic plasticity. These markers have been implicated in neuropsychiatric disorders, including major depression. However, no particular studies of EGF and FGF-2 have been conducted in older adults with major depressive disorder (MDD). In this study, we aim to investigate the plasma levels of EGF and FGF-2 in elderly with MDD. We included 89 older adults with MDD and 51 older (healthy control, HC) adults. The cognitive performance was evaluated by the Mattis Dementia Rating Scale (MDRS). The EGF and FGF-2 were measured by using multiplex assay for LUMINEX platform. There were also no significant differences between the patient group in terms of plasma levels of EGF and FGF-2 when compared to the HC group. There were not any significant correlations between plasma levels of EGF or FGF2 and MDRS total or individual scores in patient group and HC. There were significant correlations between plasma levels of EGF and FGF2 in both patient group and HC. Further study on plasma levels of EGF and FGF2 should be implemented in larger samples in elderly with MDD.
