Serum exosomal miR-103a-3p from patients with depression inhibits neuronal differentiation and promotes depressive behaviors in male rats

Abstract

Exosomes have been identified to be involved in the pathogenesis of depression. This study the effect of exosomes isolated from the serum of patients with major depressive disorder on neuronal differentiation and the molecular mechanism. PC12 cells were treated with nerve growth factor (NGF), and neuronal differentiation was analyzed using microscopy. Synaptophysin (SYP) and nestin levels were measured by reverse transcription-quantitative polymerase chain reaction, western blot, and immunofluorescence. The depression rat model was established with chronic unpredictable mild stress (CUMS) to assess the effect of exosomal miRNA on depression-like behaviors. The results showed that exosomes inhibited NGF-induced differentiation of PC12 cells and increased miR-103a-3p expression in PC12 cells. Similarly, miR-103a-3p inhibited PC12 cell differentiation. Brain-derived neurotrophic factor (BDNF) acted as a target of miR-103a-3p that reversed the differentiation induced by miR-103a-3p. Moreover, antagomir-103a-3p alleviates depressive symptoms in CUMS rats. In conclusion, exosomal miR-103-3p promotes the progression of depression by impeding neuronal differentiation via targeting BDNF, suggesting a promising therapeutic target for depression.