Abstract
Major depressive disorder (MDD) is a common mood disorder, and the treatment of MDD requires a variety of biopsychosocial approaches. The role of Silent information regulator 1 (SIRT1) in the regulation of MDD has recently been implicated. Here, we aimed to explore and elucidate the therapeutic effects of a microRNA, miR-155, in the treatment of MDD. With quantitative real-time PCR (qRT-PCR) analysis, we confirmed that cellular and serum levels of miR-155 were up-regulated in individuals with depression compared with those in healthy controls. TargetScan analysis indicated that SIRT1 is a target of miR-155, which was confirmed by dual-luciferase assay, qRT-PCR and Western blot analyses. Treatment of human neural progenitor cells with the antidepressant drug citalopram down-regulated miR-155 expression and up-regulated SIRT1 expression. These results suggest that miR-155 is an important factor in the pathophysiology of depression. miR-155 is a potential target for the development of new antidepressant treatments.
Highlights
Major depression disorder (MDD) is a mood disorder that affects almost 350 million people worldwide
Silent information regulator 1 (SIRT1) was first identified in Han Chinese women as a MDD-related gene in a clinical trial conducted by CONVERGE (China, Oxford and Virginia Common-wealth University Experimental Research on Genetic Epidemiology) [5], whereby MDD patients were shown to possess a marked down-regulation of SIRT1 in blood samples
With the aim to screen for a SIRT1-targeting miRNA associated with MDD, we compared the expression of eight candidate miRNAs, including hsa-miR-30e, hsa-miR-132, hsa-miR-135b, hsa-miR-155b, hsa-miR-181b, hsa-miR-199b, hsa-miR-448 and hsa-miR-543, in the blood samples of healthy and MDD patients
Summary
Major depression disorder (MDD) is a mood disorder that affects almost 350 million people worldwide. Evidenced by the rising suicide rates caused by depression, MDD is increasingly becoming a threatening public health problem [1]. MDD is symptomized by the lack of interest and pleasure in daily activities, worthless feeling and recurrent suicidal thoughts [2]. Neurobiological underpinnings of MDD have been the subjects of investigation [3], but the cellular and molecular mechanisms of MDD have yet to be understood. The dysregulated SIRT1 signaling plays an important role in depression-like behaviors [6,7]. Resveratrol, an antidepressant known to improve hyperanxiety status and attenuate depression-like behaviors [8], was demonstrated to activate SIRT1 [9]. The precise mechanism of SIRT1 regulation by antidepressants still remains unclear
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