Abstract
At present, due to the increasing pressures on society and the stress of everyday living, the number of individuals suffering from depression has increased. Therefore, the treatment of depression has also received increasing attention. MicroRNA (miRNA/miR)-135a is a well-studied miRNA. It has been reported that miR-135a is significantly downregulated in patients with depression and may be a potential marker for the diagnosis of the condition. However, the specific mechanisms of action of miR-135a in patients with depression remain unclear. In the present study, it was found that miR-135a was downregulated in patients with depression, and in a mouse model of depression. The effects of miR-135a on depression-related symptoms in mice were then explored. In the mice with chronic unpredictable mild stress (CUMS) that were treated with miR-135a for 3 weeks, a significantly reduced level of weight gain was observed in comparison with the control group. In addition, treatment with miR-135a mimic significantly increased sucrose preference in the sucrose preference test in the mice, and reduced the immobility time in the forced swimming test and tail suspension test. Treatment with miR-135a mimic also inhibited CUMS-induced hippocampal cell apoptosis. Furthermore, treatment with miR-135a mimic and fluoxetine significantly reduced the CUMS-induced increase in the expression levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in the hippocampus of the mice. Subsequently, reverse transcription-quantitative polymerase chain reaction and western blot analysis revealed that treatment with miR-135a mimic significantly inhibited the expression of Toll-like receptor 4 in the mouse hippocampus. In conclusion, the findings of the present study indicate that miR-135a may be a novel potential target for the treatment of depression.