Sevoflurane exposure may cause dysplasia of dendritic spines and result in fine motor dysfunction in developing mouse through the PI3K/AKT/mTOR pathway.
Sevoflurane exposure may cause dysplasia of dendritic spines and result in fine motor dysfunction in developing mouse through the PI3K/AKT/mTOR pathway.
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七氟醚暴露可能导致树突棘发育不良，并通过 PI3K/AKT/mTOR 通路导致发育中小鼠的精细运动功能障碍
DOI：
10.3389/fnins.2022.1006175
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发表时间：
2022
影响因子：
4.3
通讯作者：
Jiang, Hong
中科院分区：
文献类型：
--
作者：
Zhong, Linhong;Ma, Xiaofan;Niu, Yixuan;Zhang, Lei;Xue, Zhenyu;Yan, Jia;Jiang, Hong
七氟醚已成为小儿外科手术中使用最广泛的挥发性麻醉剂之一。然而，七氟醚暴露可能会干扰树突发育和突触发生，导致大脑功能受损。 PI3K/AKT/mTOR 通路在树突发育和突触可塑性中发挥重要作用。在这里，我们研究了七氟醚暴露是否会影响发育中小鼠树突棘的形态比例，并探讨了树突棘可塑性变化在七氟醚诱导的神经发育毒性中的作用。还检查了相关的信号通路。 C57BL/6 小鼠在出生后第 7 天（PND）暴露于 2% 七氟醚 3 小时。在 PND7 暴露七氟烷或 O2 之前 30 分钟，腹膜内注射 PI3k/AKT/mTOR 激动剂 IGF-1 或 mTOR 磷酸化抑制剂 KU0063794。暴露于七氟醚后 6 小时收获海马。采用Western blotting检测PI3K/AKT/mTOR通路磷酸化蛋白的表达。 PND14时，采集各组大脑进行高尔基体染色，并通过油镜观察海马神经元树突棘形态。当小鼠生长到青春期（PND48）时，通过平衡木步行测试来测量精细运动功能。在这里，我们发现暴露于 2% 七氟醚 3 小时会降低细树突棘的比例并增加蘑菇树突棘的比例，但不会改变树突棘的密度。七氟烷暴露还抑制未成熟小鼠海马中 PI3K/AKT/mTOR 通路的磷酸化，最终导致长期精细运动功能障碍。同时，IGF-1预处理可以挽救，KU0063794预处理可以加重七氟烷引起的损伤。总之，七氟烷暴露可能通过影响PI3K/AKT/mTOR通路的磷酸化表达而导致树突棘类型比例的变化，最终导致发育中小鼠的长期精细运动功能障碍。
Sevoflurane has become one of the most widely used volatile anesthetics in pediatric surgery. However, sevoflurane exposure may interfere with dendritic development and synaptogenesis, resulting in brain function impairment. The PI3K/AKT/mTOR pathway plays an important role in dendritic development and synaptic plasticity. Here we investigated whether sevoflurane exposure would affect the morphological proportions of dendritic spines in developing mouse and explored the role of the change of plasticity of dendritic spines in sevoflurane-induced neurodevelopmental toxicity. The related signaling pathway was also examined. C57BL/6 mice at postnatal day (PND) 7 were exposed to 2% sevoflurane for 3 h. The PI3k/AKT/mTOR agonist IGF-1 or the mTOR phosphorylation inhibitor KU0063794 was intraperitoneally injected 30 min before sevoflurane or O2 exposure at PND7. Hippocampi were harvested 6 h after sevoflurane exposure. Western blotting was applied to measure the protein expression of PI3K/AKT/mTOR pathway phosphorylation. At PND14, brains from all groups were harvested for Golgi staining, and the morphology of dendritic spines of hippocampal neurons was observed by an oil immersion lens. When the mice grew to adolescence (PND48), fine motor function was measured by the Beam walking test. Here we showed that exposure to 2% sevoflurane for 3 h decreased the proportion of thin dendritic spines and increased the proportion of mushroom dendritic spines, but not changed the density of the dendritic spines. Sevoflurane exposure also suppressed the phosphorylation of the PI3K/AKT/mTOR pathway in immature mice hippocampi, and eventually led to long-term fine motor dysfunction. Meanwhile, IGF-1 pretreatment could rescue and KU0063794 pretreatment could aggravate the impairment induced by sevoflurane. In conclusion, sevoflurane exposure may cause a change of proportions of the types of dendritic spines through impacting the phosphorylation expression of the PI3K/AKT/mTOR pathway, and eventually led to long-term fine motor dysfunction in developing mouse.
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影响因子：
3.8
作者：
Liu, Bin;Ou, Guoyao;Zhang, Jun
通讯作者：
Zhang, Jun
影响因子：
3.5
作者：
Liao, Zhaoxia;Huang, Zeqi;Li, Yujuan
通讯作者：
Li, Yujuan
影响因子：
4.7
作者：
Lee, Cheng-Che;Huang, Chiung-Chun;Hsu, Kuei-Sen
通讯作者：
Hsu, Kuei-Sen
影响因子：
5.6
作者：
Kim KY;Park KI;Kim SH;Yu SN;Park SG;Kim YW;Seo YK;Ma JY;Ahn SC
通讯作者：
Ahn SC
DOI：
10.2147/dddt.s158313
发表时间：
2018
期刊：
Drug design, development and therapy
影响因子：
--
作者：
He H;Liu W;Zhou Y;Liu Y;Weng P;Li Y;Fu H
通讯作者：
Fu H