Expressão do microRNA 184 em idosos com depressão maior: uma perspectiva translacional

Abstract

Late-life depression (LLD) is the most common psychiatric disorder and causes severe consequences in elderly. The biological mechanisms involved in LLD are complex and involve many genes. MicroRNAs (miRNAs) are small noncoding RNAs and post-translational regulators of gene expression. Imbalance in miRNAs expression is related to many diseases, including LLD. Our aim was to evaluate plasma miRNAs that are associated with LLD and possibly with the severity of depressive symptoms and cognitive performance in these individuals. A total of 116 older adults (63 with LLD and 53 elderly controls) were randomly split into discovery and validation set, using next generation sequencing (NGS) and RT-qPCR, respectively. Drosophila melanogaster was used as a translational model to evaluate behavioral phenotypes associated to the overexpression and knockout of the ortholog of hsa-miR-184. NGS analysis found hsa-miR-184 (log2foldchange = -4,205 and p-value = 1,195e-03) and hsamiR-1-3p (log2foldchange = -3,444 and p-value = 1,3251e-02) differently expressed in LLD subjects, but only hsa-miR-184 (AUC=8378, p-value < 0.0001) was validated in an independent sample. hsa-miR-184 was significantly correlated with the severity of depressive symptoms (r=-0.425, p=0.001) and the initiation/perseverance sub-score (r=0,292, p=0,032) of the Dementia Rating Scale. The translational model showed that the knockout of the ortholog of hsamiR-184 impaired locomotor and memory performance. These results suggest that hsa-miR-184 may play a significant physiopathological role in LLD.