Maternal sevoflurane exposure disrupts oligodendrocyte myelination of the postnatal hippocampus and induces cognitive and motor impairments in offspring
Maternal sevoflurane exposure disrupts oligodendrocyte myelination of the postnatal hippocampus and induces cognitive and motor impairments in offspring
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DOI：
10.1016/j.bbrc.2022.05.037
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发表时间：
2022-05-19
影响因子：
3.1
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Fan, Ze;Liang, Lirong;Zhang, Hui
母亲暴露于麻醉剂可能会对婴儿发育中的大脑造成重大的神经认知风险。由少突胶质细胞（oligodendrocytes，OLs）产生的髓鞘是脑发育所必需的。然而，全身麻醉对OLs的发育和髓鞘形成的具体影响仍然是难以捉摸的。在这项研究中，我们的目的是调查出生后的髓鞘形成和神经行为后，母亲暴露于七氟烷。用2.5%七氟烷（97.5% O2）麻醉妊娠C57 BL/6 J小鼠（妊娠第15.5天）6 h。采用新物体识别、Morris水迷宫和加速旋转棒实验评价子代小鼠的认知功能和运动协调能力。采用免疫组化、qRT-PCR、western blotting和电镜技术分析海马OLs的髓鞘形成和发育。用电生理学方法测定髓鞘功能。结果表明，妊娠期七氟醚麻醉可导致子代小鼠认知和运动功能障碍，并伴有髓鞘结构的损伤和髓鞘相关基因和蛋白（包括MBP、Olig 1、PDGFRa、Sox 10等）的下调。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，母体七氟烷暴露可能对后代的认知和运动功能产生有害影响，这可能与海马中OL的髓鞘形成中断有关。
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% O2) 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, PDGFRa, 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.