• Neuroscience · Feb 2024

    Extracellular vesicles from neural stem cells carry microRNA-16-5p to reduce corticosterone-induced neuronal injury in depression rats.

    • Xiao-Li Min, Hai-Jing Liu, Xing-Kui Dou, Fei-Xiong Chen, Qing Zhao, Xiao-Hong Zhao, Ying Shi, Qun-Yuan Zhao, Sheng-Jie Sun, Zhen Wang, and Si-Hang Yu.
    • Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: XiaoliMin121@163.com.
    • Neuroscience. 2024 Feb 6; 538: 9510995-109.

    ObjectiveDepression is a common mental illness. Neural stem cell-derived extracellular vesicles (NSC-EVs) are involved in repairing neuronal injury. We estimated the mechanism of miR-16-5p in depression rats.MethodsEVs were extracted from NSCs. The depression rat model was established by corticosterone (CORT) induction and treated with NSC-EVs. The depression behavioral/pathological changes in rats were assessed using forced swimming test, open field test, sucrose consumption test and western blotting. The neuronal apoptosis in hippocampal tissue were detected. CORT-induced PC12 cell model was established. EV uptake by PC12 cells was measured and PC12 cell apoptosis was detected. The downstream targets of miR-16-5p were predicted and verified. The expressions of miR-16-5p and MYB in rats, PC12 cells, and EVs were measured. Functional rescue experiments were conducted to verify the role of miR-16-5p and MYB in PC12 cell apoptosis.ResultsCORT induction increased neuronal apoptosis in hippocampal tissue and induced depression-like behaviors in rats, while NSC-EV treatment improved depression-like behaviors and apoptosis in rats. In PC12 cells, NSC-EVs decreased CORT-induced PC12 cell apoptosis. NSC-EVs carried miR-16-5p into PC12 cells. miR-16-5p knockdown in EVs partially reversed the inhibitory effects of NSC-EVs on CORT-induced PC12 cell apoptosis. miR-16-5p targeted to inhibit MYB to repress CORT-induced PC12 cell apoptosis. In vivo experiments further verified that NSC-EVs reduced neuronal injury in CORT-induced depression rats via the miR-16-5p/MYB axis.ConclusionNSC-EVs-mediated alleviation on neuronal injury by carrying miR-16-5p to target MYB was highly likely one of the mechanisms by which NSC-EVs mediated miR-16-5p in neuroprotection of depression rats.Copyright © 2023 IBRO. Published by Elsevier Inc. All rights reserved.

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