Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis

摘要: Exosomal microRNAs (miRNAs) have been suggested to participate in the pathogenesis of neuropsychiatric diseases, but their role major depressive disorder (MDD) is unknown. We performed a genome-wide miRNA expression profiling blood-derived exosomes from MDD patients and control subjects revealed top differentially expressed exosomal miRNA, i.e. hsa-miR-139-5p (upregulation), had good performance differentiate between controls. Tail vein injection blood isolated into normal mice caused depressive-like behaviors as determined by forced swimming, tail suspension, novelty suppressed feeding tests, healthy volunteers unpredictable mild stress (CUMS)-treated alleviated behaviors. CUMS also showed significantly increased brain levels miR-139-5p. Furthermore, CUMS-treated were rescued intranasal miR-139-5p antagomir, suggesting that may mediate stress-induced depression-like behavior mice. Both exosome treatment antagomir hippocampal neurogenesis mice, decreased The was validated vitro experiments, demonstrating negative regulator for neural stem cell proliferation neuronal differentiation. Our findings together suggest with depression involvement miR-139-5p-regulated neurogenesis. Therefore, miRNAs are promising targets diagnosis MDD.