Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice
Abstract As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult b...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85834-1 |
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| author | Linyong Zhang Zhidan Ke Ning Zhang Dechuan Wang Liang Zhou |
| author_facet | Linyong Zhang Zhidan Ke Ning Zhang Dechuan Wang Liang Zhou |
| author_sort | Linyong Zhang |
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| description | Abstract As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult brain is barely discovered. Here, we show that repeated sevoflurane exposure, but not single exposure, causes hypomyelination and abnormal ultrastructure of myelin sheath in the prefrontal cortex (PFC) of adult male mice, which is considered as a critical brain region for general anesthesia mediated consciousness change. Furthermore, disrupted proliferation of oligodendrocyte precursor cells (OPCs) contributes to repeated sevoflurane exposure-induced myelin defect. This may be owing to an accumulated tuberous sclerosis complex 1 (TSC1) expression and inhibition of mammalian target of rapamycin (mTOR) signaling, leading to the unbalance of TSC1-mTORC1 activity after repeated sevoflurane exposure, which is critical for proper myelination of the central nervous system (CNS). Moreover, repeated sevoflurane exposure aggregates myelination defect in the cuprizone-induced demyelination model. Together, our present work establishes the role of sevoflurane exposure in myelin integrity in the PFC of the adult male mice and provides a new insight to elucidate the mechanism of GAs-induced brain dysfunctions. |
| format | Article |
| id | doaj-art-49d25591d09d43cfaf843f9f30839caf |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-49d25591d09d43cfaf843f9f30839caf2025-08-20T02:35:39ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85834-1Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male miceLinyong Zhang0Zhidan Ke1Ning Zhang2Dechuan Wang3Liang Zhou4Department of Anesthesiology, Affiliated Hospital of Zunyi Medical UniversityKey Laboratory of Anesthesia and Organ Protection (Zunyi Medical University), Ministry of Education, Zunyi Medical UniversityKey Laboratory of Anesthesia and Organ Protection (Zunyi Medical University), Ministry of Education, Zunyi Medical UniversityDepartment of Anesthesiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Anesthesiology, Affiliated Hospital of Zunyi Medical UniversityAbstract As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult brain is barely discovered. Here, we show that repeated sevoflurane exposure, but not single exposure, causes hypomyelination and abnormal ultrastructure of myelin sheath in the prefrontal cortex (PFC) of adult male mice, which is considered as a critical brain region for general anesthesia mediated consciousness change. Furthermore, disrupted proliferation of oligodendrocyte precursor cells (OPCs) contributes to repeated sevoflurane exposure-induced myelin defect. This may be owing to an accumulated tuberous sclerosis complex 1 (TSC1) expression and inhibition of mammalian target of rapamycin (mTOR) signaling, leading to the unbalance of TSC1-mTORC1 activity after repeated sevoflurane exposure, which is critical for proper myelination of the central nervous system (CNS). Moreover, repeated sevoflurane exposure aggregates myelination defect in the cuprizone-induced demyelination model. Together, our present work establishes the role of sevoflurane exposure in myelin integrity in the PFC of the adult male mice and provides a new insight to elucidate the mechanism of GAs-induced brain dysfunctions.https://doi.org/10.1038/s41598-025-85834-1SevofluraneRepeated exposureMyelinationOligodendrocyteMTORC1 |
| spellingShingle | Linyong Zhang Zhidan Ke Ning Zhang Dechuan Wang Liang Zhou Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice Scientific Reports Sevoflurane Repeated exposure Myelination Oligodendrocyte MTORC1 |
| title | Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice |
| title_full | Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice |
| title_fullStr | Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice |
| title_full_unstemmed | Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice |
| title_short | Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice |
| title_sort | repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice |
| topic | Sevoflurane Repeated exposure Myelination Oligodendrocyte MTORC1 |
| url | https://doi.org/10.1038/s41598-025-85834-1 |
| work_keys_str_mv | AT linyongzhang repeatedsevofluraneexposurecauseshypomyelinationintheprefrontalcortexofadultmalemice AT zhidanke repeatedsevofluraneexposurecauseshypomyelinationintheprefrontalcortexofadultmalemice AT ningzhang repeatedsevofluraneexposurecauseshypomyelinationintheprefrontalcortexofadultmalemice AT dechuanwang repeatedsevofluraneexposurecauseshypomyelinationintheprefrontalcortexofadultmalemice AT liangzhou repeatedsevofluraneexposurecauseshypomyelinationintheprefrontalcortexofadultmalemice |