Sevoflurane Induces a Cyclophilin D-Dependent Decrease of Neural Progenitor Cells Migration.

Sevoflurane Induces a Cyclophilin D-Dependent Decrease of Neural Progenitor Cells Migration.
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七氟醚诱导亲环素D依赖的神经前体细胞迁移减少。

DOI:
10.3390/ijms24076746
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发表时间:
2023-04-04
影响因子:
5.6
通讯作者:
Zhang, Yiying
Zhang, Yiying
中科院分区:
生物学2区
文献类型:
--
作者:
Lu, Pan;Liang, Feng;Dong, Yuanlin;Xie, Zhongcong;Zhang, Yiying

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临床研究表明,年轻时反复暴露于麻醉和手术可能会增加认知障碍的风险。我们之前的研究表明,七氟烷可通过改变亲环素D(CypD)水平和线粒体功能影响幼龄动物的神经发生和认知功能。神经祖细胞(NPC)迁移与发育中大脑的认知功能有关。然而,尚不清楚七氟烷是否可以通过CypD的变化调节NPC迁移。为了解决这个问题,我们用七氟烷处理了从野生型(WT)和CypD敲除(KO)小鼠以及年幼的WT和CypD KO小鼠中收获的NPC。我们使用免疫荧光染色、伤口愈合试验、transwell试验、质谱法和蛋白质印迹法评估七氟烷对CypD、活性氧(ROS)、双皮质素水平和NPC迁移的影响。我们发现,七氟烷增加CypD和ROS的水平,降低双皮质素的水平,并减少在体外和WT幼龄小鼠中从WT小鼠中收获的NPC的迁移。CypD的KO减弱了这些作用,表明七氟烷诱导的NPC迁移减少依赖于CypD。我们的研究结果为今后的研究建立了一个系统,旨在探索七氟烷麻醉对NPC迁移损伤的影响。
Clinical studies have suggested that repeated exposure to anesthesia and surgery at a young age may increase the risk of cognitive impairment. Our previous research has shown that sevoflurane can affect neurogenesis and cognitive function in young animals by altering cyclophilin D (CypD) levels and mitochondrial function. Neural progenitor cells (NPCs) migration is associated with cognitive function in developing brains. However, it is unclear whether sevoflurane can regulate NPCs migration via changes in CypD. To address this question, we treated NPCs harvested from wild-type (WT) and CypD knockout (KO) mice and young WT and CypD KO mice with sevoflurane. We used immunofluorescence staining, wound healing assay, transwell assay, mass spectrometry, and Western blot to assess the effects of sevoflurane on CypD, reactive oxygen species (ROS), doublecortin levels, and NPCs migration. We showed that sevoflurane increased levels of CypD and ROS, decreased levels of doublecortin, and reduced migration of NPCs harvested from WT mice in vitro and in WT young mice. KO of CypD attenuated these effects, suggesting that a sevoflurane-induced decrease in NPCs migration is dependent on CypD. Our findings have established a system for future studies aimed at exploring the impacts of sevoflurane anesthesia on the impairment of NPCs migration.
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