Aims: To explore the role of miR-124 in depression and its potential targets. Background: Depression is one of the most common mental illnesses, and symptoms include depression, decreased interest, and severe cases with suicidal tendencies. Objective: As a brain-specific microRNA, the mechanism of miR-124 in depression has not been clarified. The present study aimed to explore the role of miR-124 in depression and its potential targets. Methods: The depression model was first replicated by the chronic unpredictable mild stress (CUMS) method. miR-124 antagomir was injected into the hippocampus of CUMS rats. Sucrose preference test (SPT), open-field test (OFT), elevated-plus maze (EPM), and forced swimming test (FST) were used to analyze the depression-like behavior. The content of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in hypothalamus was analyzed by ELISA. qRT-PCR and western blot assay were used to functional analysis. Results: miR-124 expression was up-regulated in the hippocampus of CUMS -induced depression model rats, while CREB1 and BDNF were down-regulated. Administration of miR-124 antagomir in hippocampus inhibited miR-124 expression in hippocampus of CUMS rats. Additionally, SPT, OFT, EPM, and FST also showed that miR-124 antagomir can reduce the depression-like behavior of CUMS rats. Furthermore, miR-124 antagomir injection increased the levels of NE, DA and 5-HT in the hypothalamus of CUMS rats. Moreover, miR-124 antagomir injection increased the expression of cyclic AMP-responsive element binding protein1 (CREB1) and brain-derived neurotrophic factor (BDNF) in hippocampus. Using a dual luciferase reporter assay, it was confirmed that miR-124 directly targets the 3'UTR of CREB1 and BDNF genes. Conclusion: Knockdown of miR-124 can improve depression-like behavior in CUMS-induced depressive rats, which may be related at least in part to the up-regulation of CREB1 and BDNF expression in the hippocampus.

Background Current evidence demonstrates that blood glucose fluctuation can be associated with depression and anxiety. The association among blood glucose fluctuation, traditional risk factors and emotional disorders in T2DM should be studied and clarified. Methods A total of 182 diabetic patients including 81 patients with depression or anxiety and 101 patients without emotional disorder were enrolled into this study. Data were obtained through medical history and questionnaire survey. Data were analyzed using appropriate statistical methods. Results The comparison results of basic information between the two groups showed that the differences of the proportion of female were statistically significant ( p = 0.002). There was no statistical difference in laboratory examination indexes between the two groups, however, standard deviation of blood glucose (SDBG) and postprandial glucose excursion (PPGE) of the comorbidity group were significantly higher than that of control group ( p = 0.032 and p = 0.037). The results of questionnaire survey showed that there were statistically significant differences in sleep quality, PSQI and dietary habit between the two groups ( p < 0.001, p < 0.001 and p < 0.001). Stratified analysis results according to gender showed that the percentage of cognitive disorder, anxiety and depression in female group was significantly higher than that in male group ( p = 0.001, p < 0.001 and p < 0.001). Mini-mental state examination (MMSE), self-rating anxiety scale (SAS) and patient health questionnaire (PHQ-9) score in female group were also higher than male group ( p = 0.001, p < 0.001 and p < 0.001). Logistic regression analysis results showed that SDBG and sleep quality were associated with emotional disorders in T2DM ( p = 0.040 and p < 0.001) and the OR values of these factors were 7.588 (1.097–52.069) and 4.428 (2.649–7.401). Conclusions Blood glucose fluctuation and sleep quality are associated with the increased prevalence of depression and anxiety disorders in T2DM.

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