Expression Of BDNF And CREB1-related Micro RNAs In Peripheral Blood Mononuclear Cells Of Patients With Major Depressive Disorder

ObjectivesMicroRNAs are a newly discovered class of posttranscriptional regulatory molecules that can support survival of neurons, and regulate neurogenesis and synaptic functions. Thus, unsurprisingly, mi RNAs may play a key role in central nervous system.In recent years, increasing evidence has suggested that the expression of mi RNAs is altered in the brain of animal models of depression, and in human postmortem brain, peripheral tissue of the patients with depression. In addition, it has been reported that the expression levels of mi RNAs can be modulated by the antidepressant treatment.Mi R-124、mi R-132 and mi R-134 are the most abundant mi RNAs in the CNS. Interestingly, these three mi RNAs could regulate the expression of BDNF and/or CREB1 at the posttranscriptional level, according to the published literature for reports on mi RNAs associated with BDNF and CREB1, and some classical software for mi RNA target prediction available online. Of note, it has already been shown that BDNF and CREB1 are involved in the pathogenesis of depression and the mechanism of action of antidepressants. It is therefore likely that these three mi RNAs also play a role in the mechanism of depression and their treatment.The aim of the current study was to investigate whether the expression of mi R-124, mi R-132 and mi R-134 were associated with patients with major depressive disorder(MDD) and the mechanism of action of antidepressants.MethodsThe expression levels of mi R-132, mi R-134 and mi R-132 were examined in 32 pre-and post-treatment MDD patients during 8-week antidepressant treatment, and 30 healthy controls, using Taqman real-time quantitative reverse transcription polymerase chain reaction(q RT-PCR). Severity of the depressive symptoms in patients was evaluated using the 24-item Hamilton Depression Rating Scale(HAMD-24) at baseline and after the 8-week treatment. Depending on the results of Shapiro-Wilk test of normality, the difference between three mi RNAs in patients before treatment and controls were evaluated by Mann-Whitney U-test. Moreover, the Wilcoxon test for paired samples were used for analyzing mi R-124 and mi R-134 expression levels and HAMD-24 scores in pre and post-treatment MDD groups. The paired sample t test was used for analyzing mi R-132 expression levels in pre and post-treatment MDD groups. The relationship between mi RNAs expression levels and clinical variables were assessed using Spearman’s or Pearson correlation coefficient when appropriate.Results1. The mi R-124 expression levels in PBMC of patients with major depressive disorder were significantly higher than those in healthy controls. However, both the mi R-132 and mi R-134 expression levels in PBMC were not significantly different between patients group and healthy controls group. In addition, baseline mi R-124 levels were not significantly correlated with baseline total HDRS scores(r=-0.07,p=0.705), and with reduction of total HDRS scores in all patients between two visits(r=-0.029,p=0.874).2. The mi R-124 expression levels in PBMC of patients decreased significantly after 8 weeks antidepressant treatment compared with baseline measurements(p=0.0004). In addition, the mi R-132 expression levels increased significantly after 8 weeks treatment(p=0.025). Howover, the mi R-134 expression levels did not significantly change after the 8 weeks of antidepressant treatment(p=0.1). The changes in mi R-124 and mi R-132 expression levels in patients were not significantly correlated with the reduction in total HAMD-24 scores during the 8-week treatment(r=-0.029,p=0.874; r=-0.199,p=0.276, respectively).Conclusions1. The results indicate that mi R-124 may contribute to the pathophysiology of major depressive disorder and the mechanism of action of antidepressants. Furthermore, mi R-124 could be used as a state-related peripheral biomarker for MDD and a potential drug targets for antidepressants.2. The increased mi R-132 expression levels in PBMC of patients after antidepressant treatment indicates that mi R-132 may contribute to the mechanism of action of antidepressants. Also, mi R-132 may be used as a potential drug targets for antidepressants.