Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States of America.
PLoS One. 2019 May 20;14(5):e0216372. doi: 10.1371/journal.pone.0216372. eCollection 2019.
Anesthesia may induce neurotoxicity and neurocognitive impairment in young mice. However, the underlying mechanism remains largely to be determined. Meanwhile, autophagy is involved in brain development and contributes to neurodegenerative diseases. We, therefore, set out to determine the effects of sevoflurane on autophagy in the hippocampus of young mice and on cognitive function in the mice.
Six day-old mice received 3% sevoflurane, for two hours daily, on postnatal days (P) 6, 7 and 8. We then decapitated the mice and harvested the hippocampus of the young mice at P8. The level of LC3, the ratio of LC3-II to LC3-I, and SQSTM1/p62 level associated with the autophagy in the hippocampus of the mice were assessed by using Western blotting. We used different groups of mice for behavioral testing via the Morris Water Maze from P31 to P37.
The anesthetic sevoflurane increased the level of LC3-II and ratio of LC3-II/LC3-I, decreased the p62 level in the hippocampus of the young mice, and induced cognitive impairment in the mice. 3-Methyladenine, the inhibitor of autophagy, attenuated the activation of autophagy and ameliorated the cognitive impairment induced by sevoflurane in the young mice.
These data showed that sevoflurane anesthesia might induce cognitive impairment in the young mice via activation of autophagy in the hippocampus of the young mice. These findings from the proof of concept studies have established a system and suggest the role of autophagy in anesthesia neurotoxicity and cognitive impairment in the young mice, pending further investigation.
麻醉可能会导致幼鼠的神经毒性和神经认知功能障碍。然而，其潜在机制在很大程度上仍有待确定。同时，自噬参与脑发育，并有助于神经退行性疾病。因此，我们着手研究七氟醚对幼鼠海马自噬和认知功能的影响。
6 日龄幼鼠在生后第 6、7 和 8 天，每天接受 3%七氟醚麻醉 2 小时。然后断头处死幼鼠，取 P8 海马。通过 Western blot 检测幼鼠海马中 LC3、LC3-II/LC3-I 比值和 SQSTM1/p62 水平与自噬相关的指标。我们使用不同组别的幼鼠通过 Morris 水迷宫行为测试，从 P31 到 P37 进行行为测试。
麻醉剂七氟醚增加了 LC3-II 的水平和 LC3-II/LC3-I 的比值，降低了幼鼠海马中的 p62 水平，并导致幼鼠认知功能障碍。自噬抑制剂 3-甲基腺嘌呤减弱了自噬的激活，并改善了七氟醚诱导的幼鼠认知障碍。
这些数据表明，七氟醚麻醉可能通过激活幼鼠海马中的自噬导致幼鼠认知障碍。这些来自概念验证研究的数据建立了一个系统，并提示自噬在幼鼠麻醉神经毒性和认知障碍中的作用，有待进一步研究。
