Differential serum exosome microRNA profile in a stress-induced depression rat model

BACKGROUND: Increasing evidence has shown the important role of exosomes in the maintenance of brain function and pathogenesis of brain disease, but little is known about their association with depression. The aim of this project was to explore the miRNA profile of exosomes in the serum of rats with depression induced by chronic unpredictable mild stress (CUMS). METHODS: A rat model of depression was replicated via CUMS. Behavioral performance was observed, and serum exosomes were isolated and identified. The protein expression levels of brain-derived neurotrophic factor (BDNF), TrkB, and synaptotagmin 1 in the hippocampus, prefrontal cortex (PFC), and serum exosomes were measured. GO and KEGG enrichment analysis of differential genes was carried out using the R package clusterProfiler. RESULTS: The CUMS rats showed depression-like behaviors, together with decreased expression levels of BDNF, TrkB, and synaptotagmin 1 in the hippocampus, PFC, and serum exosomes. GO and KEGG enrichment analysis indicated that the differential expression of miRNAs might play an important role in the pathogenesis of stress-induced depression through the MAPK pathway, Wnt pathway, and mTOR pathway. LIMITATIONS: The protein expression levels of BDNF, TrkB, and synaptotagmin 1 were measured only in the hippocampus and PFC. The function of the differentially expressed miRNAs was not verified in the animal model, which should be investigated in detail in future studies. CONCLUSIONS: The miRNA profile was altered in rats with stress-induced depression, which might be con-sidered a potential biomarker for the early diagnosis of depression.