Myelination Trajectory and Microglial Dynamics Following Repeated Sevoflurane Exposure in Developing Brain

IF 5.1 2区医学 Q1 NEUROSCIENCES

Glia Pub Date : 2025-02-10 DOI:10.1002/glia.70000

Ji Che, Yuanyuan Wu, Jing Dong, Xuliang Jiang, Li Yang, Yali Chen, Jun Zhang

{"title":"Myelination Trajectory and Microglial Dynamics Following Repeated Sevoflurane Exposure in Developing Brain","authors":"Ji Che, Yuanyuan Wu, Jing Dong, Xuliang Jiang, Li Yang, Yali Chen, Jun Zhang","doi":"10.1002/glia.70000","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>The myelination is a critical process during brain development. This study aimed to explore the impact of volatile anesthetic sevoflurane on developing myelination and the role of microglial activation in this process. Neonatal C57BL/6J mice were exposed to sevoflurane at their postnatal 6–8 days. Neurobehavioral tests were used to assess fine motor and cognitive functions. Myelination of hippocampus (HC) and corpus callosum (CC), as well as microglial activation, were determined by western blotting and immunostaining. Lipid droplets were assessed by Oil-Red-O and Bodipy staining. Further, primary microglia were co-cultured with oligodendrocyte precursor cell (OPC) to determine the role of microglia in the proliferation and differentiation of OPC. And microglial inhibitor minocycline and CSF1R inhibitor PLX5622 were administered to assess the effects of microglial activation on developing myelination. The results showed that repeated sevoflurane exposure impaired both fine motor and cognitive functions and induced abnormal expressions of myelin-related proteins myelin basic protein (MBP) and platelet-derived growth factor α receptor (PDGFR-α). And accumulations of lipid droplets were found in the microglia of HC and CC after sevoflurane exposure. Further, the spatiotemporal response to repeated sevoflurane exposure in glial cells exhibited an aberrant myelination process and microglial polarization. The conditioned medium from sevoflurane-treated microglia inhibited the OPC proliferation and differentiation, while minocycline or PLX5622 alleviated sevoflurane-induced neuroinflammation and hypomyelination. Therefore, repeated sevoflurane exposure negatively affected OPC differentiation and myelination trajectory through hyperactivating microglia in developing brain, leading to motor and cognitive impairments, while microglial inhibition/depletion could protect against sevoflurane-induced damage on developing myelination.</p>\n </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 6","pages":"1221-1240"},"PeriodicalIF":5.1000,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Glia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/glia.70000","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

The myelination is a critical process during brain development. This study aimed to explore the impact of volatile anesthetic sevoflurane on developing myelination and the role of microglial activation in this process. Neonatal C57BL/6J mice were exposed to sevoflurane at their postnatal 6–8 days. Neurobehavioral tests were used to assess fine motor and cognitive functions. Myelination of hippocampus (HC) and corpus callosum (CC), as well as microglial activation, were determined by western blotting and immunostaining. Lipid droplets were assessed by Oil-Red-O and Bodipy staining. Further, primary microglia were co-cultured with oligodendrocyte precursor cell (OPC) to determine the role of microglia in the proliferation and differentiation of OPC. And microglial inhibitor minocycline and CSF1R inhibitor PLX5622 were administered to assess the effects of microglial activation on developing myelination. The results showed that repeated sevoflurane exposure impaired both fine motor and cognitive functions and induced abnormal expressions of myelin-related proteins myelin basic protein (MBP) and platelet-derived growth factor α receptor (PDGFR-α). And accumulations of lipid droplets were found in the microglia of HC and CC after sevoflurane exposure. Further, the spatiotemporal response to repeated sevoflurane exposure in glial cells exhibited an aberrant myelination process and microglial polarization. The conditioned medium from sevoflurane-treated microglia inhibited the OPC proliferation and differentiation, while minocycline or PLX5622 alleviated sevoflurane-induced neuroinflammation and hypomyelination. Therefore, repeated sevoflurane exposure negatively affected OPC differentiation and myelination trajectory through hyperactivating microglia in developing brain, leading to motor and cognitive impairments, while microglial inhibition/depletion could protect against sevoflurane-induced damage on developing myelination.

查看原文本刊更多论文

反复暴露于七氟醚后发育中的大脑髓鞘形成轨迹和小胶质动力学。

髓鞘形成是大脑发育的重要过程。本研究旨在探讨挥发性麻醉剂七氟醚对髓鞘形成的影响以及小胶质细胞激活在这一过程中的作用。新生C57BL/6J小鼠在出生后6-8天暴露于七氟醚。神经行为测试用于评估精细运动和认知功能。western blotting和免疫染色检测海马（HC）和胼胝体（CC）的髓鞘形成以及小胶质细胞的激活情况。采用Oil-Red-O和Bodipy染色法测定脂滴。进一步，我们将小胶质细胞与少突胶质细胞前体细胞（OPC）共培养，以确定小胶质细胞在少突胶质细胞前体细胞增殖和分化中的作用。并给予小胶质细胞抑制剂米诺环素和CSF1R抑制剂PLX5622，以评估小胶质细胞活化对髓鞘形成的影响。结果表明，反复暴露于七氟醚可导致小鼠精细运动和认知功能受损，髓鞘相关蛋白髓鞘碱性蛋白（MBP）和血小板源性生长因子α受体（PDGFR-α）表达异常。七氟醚暴露后HC和CC的小胶质细胞中均有脂滴聚集。此外，神经胶质细胞对重复七氟醚暴露的时空反应表现出异常的髓鞘形成过程和小胶质细胞极化。七氟醚处理的小胶质细胞条件培养基抑制OPC的增殖和分化，而二甲胺四环素或PLX5622则减轻七氟醚诱导的神经炎症和低髓鞘形成。因此，反复暴露于七氟醚可通过过度激活脑内小胶质细胞，对OPC分化和髓鞘形成轨迹产生负面影响，导致运动和认知障碍，而小胶质细胞抑制/耗损可保护七氟醚诱导的髓鞘形成损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Glia 医学-神经科学

CiteScore

13.10

自引率

4.80%

发文量

162

审稿时长

3-8 weeks

期刊介绍： GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.