Sevoflurane induces cognitive impairment in young mice via autophagy
Sevoflurane induces cognitive impairment in young mice via autophagy
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七氟醚通过自噬诱导幼鼠认知障碍
DOI：
10.1371/journal.pone.0216372
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发表时间：
2019-05-20
期刊：
影响因子：
3.7
通讯作者：
Xie, Zhongcong
中科院分区：
文献类型：
--
作者：
Wang, Xiaoning;Dong, Yuanlin;Xie, Zhongcong
背景麻醉可引起幼鼠神经毒性和神经认知功能障碍。然而，潜在的机制在很大程度上仍有待确定。与此同时，自噬参与了大脑的发育，并导致了神经退行性疾病。因此，我们着手确定七氟醚对幼鼠海马体自噬和对小鼠认知功能的影响。方法出生后第6、7、8天，给6天龄小鼠注射3%七氟醚，每天2小时，于出生后8天处死小鼠，取幼鼠海马区。用免疫印迹法检测与自噬相关的小鼠海马区Lc3水平、Lc3-II/Lc3-I比值和SQSTM1/p62水平。我们使用不同组的小鼠通过Morris水迷宫进行了从P31到P37的行为测试。结果七氟醚可升高幼年小鼠海马区Lc3-II水平和Lc3-II/Lc3-I比值，降低P62水平，并导致小鼠认知功能障碍。自噬抑制剂3-甲基腺嘌呤可减弱自噬的激活，改善七氟醚所致的幼鼠认知功能障碍。结论七氟醚麻醉可能通过激活幼鼠海马区的自噬功能而导致幼鼠认知功能障碍。这些来自概念验证研究的发现已经建立了一个系统，并表明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。
Background 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. Methods 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. Results 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. Conclusion 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.