微泡
污渍
RAC1
下调和上调
小RNA
外体
转染
细胞分化
细胞生物学
维甲酸
化学
生物
细胞培养
信号转导
生物化学
基因
遗传学
作者
Shengwei Wu,Zewei Chen,Zhengzheng Xuan,Yufang Zhou,Chubing Zou,Youtian Wang,Junrong Ye,Pinge Zhao,Aixiang Xiao,Lin Yu,Jianxiong Guo
标识
DOI:10.1166/jbn.2023.3527
摘要
Exosomes are associated with neuronal differentiation in mental disorders, such as depression. This study explored the effects of exosomes on neuronal differentiation and their underlying molecular mechanisms. We isolated exosomes from the sera of patients with depression. These characteristics were authenticated by TEM, NTA and western blotting. A differentiated cell model was established using all-trans retinoic acid (RA) to treat SH-SY5Y cells. Exosomes from depressed serum co-cultured with miR-96-5p mimic-transfected RA-treated cells, and PMA was used to activate RAC1. Neuronal differentiation indices were analyzed by microscopy, quantitative PCR, immunofluorescence assay, and western blotting. The results illustrated that exosomes inhibited RA-induced differentiation, downregulated SYP, upregulated nestin, and decreased SYP-positive cell number. miR-96-5p was elevated in serum-released exosomes from depressed patients, which impeded RA-induced neuronal differentiation. RAC1 is an miR-96-5p target. Activation of RAC1 partly counteracted the effects on neuronal differentiation induced by enhanced miR-96-5p levels. Additionally, decreasing miR-96-5p attenuated depression-like behaviors and promoted hippocampal neuron differentiation induced by CUMS. Summarily, serum-derived exosomes from patients with depression suppress neuronal differentiation via the miR-96-5p/RAC1 axis. Moreover, decreased miR-96-5p levels suppresses CUMS-induced depression. These consequences suggest that regulating exosomes secretion and exosomal miR-96-5p expression will be a new approach for therapy of depression.
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