State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China; Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
Biochem Biophys Res Commun. 2022 Jul 23;614:175-182. doi: 10.1016/j.bbrc.2022.05.037. Epub 2022 May 14.
Maternal exposure to anesthetic agents could impose significant neurocognitive risks on the developing brain of infants. Myelin produced by oligodendrocytes (OLs) is essential for the development of brain. However, the concrete effect of general anesthesia on the development and myelination of OLs is still elusive. In this study, we aim to investigate postnatal myelination and neural behavior after maternal exposure to sevoflurane. Pregnant C57BL/6 J mice (gestational day 15.5) were anesthetized with 2.5% sevoflurane (in 97.5% O) for 6 h. Cognitive function and motor coordination of the offspring mice were evaluated with novel object recognition, Morris water maze and accelerating rotarod tests. Myelination and development of hippocampal OLs were analyzed with immunohistochemistry, qRT-PCR, western blotting and electron microscopy. The functionality of myelin was measured with electrophysiology. Our results showed that sevoflurane anesthesia during the gestational period induced cognitive and motor impairments in offspring mice, accompanied with damages of myelin structure and down regulations of myelin-associated genes and proteins (including MBP, Olig1, PDGFRα, Sox10, etc.). The development and maturation of OLs were suppressed, and the axonal conduction velocity was declined. These results demonstrated that maternal sevoflurane exposure could induce detrimental effects on cognitive and motor functions in offspring, which might be associated with disrupted myelination of OLs in the hippocampus.
母体暴露于麻醉剂可能会对婴儿发育中的大脑造成重大神经认知风险。少突胶质细胞（OLs）产生的髓磷脂对于大脑的发育至关重要。然而，全身麻醉对 OLs 的发育和髓鞘形成的确切影响仍不清楚。在这项研究中，我们旨在研究母体暴露于七氟醚后对后代髓鞘形成和神经行为的影响。将怀孕的 C57BL/6J 小鼠（妊娠第 15.5 天）用 2.5%七氟醚（97.5% O）麻醉 6 小时。通过新物体识别、Morris 水迷宫和加速转棒测试评估后代小鼠的认知功能和运动协调能力。通过免疫组织化学、qRT-PCR、western blot 和电子显微镜分析海马 OL 髓鞘形成和发育。用电生理学测量髓鞘的功能。我们的结果表明，妊娠期七氟醚麻醉会导致后代小鼠认知和运动功能受损，同时伴有髓鞘结构损伤和髓鞘相关基因和蛋白（包括 MBP、Olig1、PDGFRα、Sox10 等）下调。OLs 的发育和成熟受到抑制，轴突传导速度下降。这些结果表明，母体暴露于七氟醚会对后代的认知和运动功能产生有害影响，这可能与海马 OLs 的髓鞘形成受损有关。
