| Background Presently, the medication is the major method of clinical antidepressant treatment, which has the obvious delayed effects. However, the sleep deprivation (SD) could quickly relieve depression. The significant efficacy of antidepressant drugs (eg. Clomipramine, a tricyclic antidepressant) on antidepressant has been confirmed in clinical trials. In recent years, clinical study found that antidepressant drugs combined with SD is effective in the treatment of depression, but its molecular mechanism is not clear. Brain derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of depression, and become one of the most important antidepressant targets. It has been reported to be an important index of the the treatment effect. It is believed that miRNAs played a decisive role on neurogenesis, and there have considerable evidences that miRNAs have a close relationship with the depression. In the present study, behavior changes and the expressions of BDNF and miR-10b in hippocampus had been investigated in chronic unpredictable stress stimulated depression-model rats after treatment by Clomipramine combined SD. Moreover, the associations of BDNF and miR-10b and their anti-depression mechanisms had also been explored in the study.Objectives To investigate the behaviors and expressions of BDNF and microRNA-10b on depression-like rats after treated with Clomipramine combinedSD, and to reveal the mechanism for antidepressant aroused by sleep deprivation from the relationship of the expression of BDNF and microRNA-10b.Methods 90 male Sprague Dawley rats were used,10 rats were inclued in control group, and 80 rats were exposed on unpredicted mild stressors for 28 consecutive days who were divided into 8 groups (depression group (10), sleep deprivation group (10), clomipramine week group (10), clomipramine weeks group (10), clomipramine three weeks group (10), sleep deprivation combined with one week clomipramine group (10), sleep deprivation combined with clomipramine two weeks group (10) sleep deprivation combined with clomipramine three weeks group (10).Then all groups were on the sucrose consumption test and the open-field test. qRT-PCR and the Western Blot (WB) were also used to test the expression of BDNF and microRNA-10b in the hippocampus. At last Dual fluorescence report method were used to detect the relationship between BDNF and microRNA-10b.Results Compared with the normal control group, the scores of depressiongroup was significantly decreased in the sucrose consumption test and the open-field test (p<0.05), and compared with the depression group, the scores of antidepressant group was significantly increased in the these two tests (p<0.05).; In qRT-PCR and WB:Compared with normal control group, the BDNF expression was significantly decreased in the hippocampus of depression group (p<0.05), while the opposite result was presented in microRNA-10b (p<0.05); and compared with the depression group, the BDNF protein expression was significantly increased of antidepressant group (p<0.05), while the opposite result was also presented in microRNA-10b (p<0.05). Double fluorescent report showed that BDNF was the targeted gene of microRNA-10b.Conclusions The rats with higher expression of BDNF had the better behavior ability, while the higher expression of microRNA-10b had the worse behavior ability.In addition, there was the negatively correlated of BDNF and microRNA-10b.Double fluorescent indicated that BDNF was the targeted gene of microRNA-10b, and that suggested sleep deprivation colud improve the depression by down-regulated microRNA-10b expression which targered BDNF and up-regulated its expression. So, we expected to fine a new cluesin studying the mechanism of antidepressant with sleep deprivation. |
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