Jia Junke, Zhu Jinpiao, Yang Qiuyue, Wang Yanlin, Zhang Zongze, Chen Chang
Department of Anesthesiology, Women's Hospital, Zhejiang University School of Medicine, Xue Shi Road, Hangzhou, Zhejiang 310002, China; Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, Hubei 430071, China.
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, Hubei 430071, China.
Neuroscience. 2020 Apr 15;432:73-83. doi: 10.1016/j.neuroscience.2020.02.023. Epub 2020 Feb 26.
The possibility that exposure to inhalation anaesthetics inhibits neurogenesis and results in memory deficits has attracted considerable interest over the past decade. This study was designed to investigate the mechanism of the sevoflurane exposure-induced decline in hippocampal neurogenesis. Young mice were anaesthetized with a gaseous mixture of 3.0% sevoflurane/60% oxygen 2 h daily for three consecutive days. Sodium butyrate (NaB) administration began 2 h prior to anaesthesia and continued daily until the end of behavioural tests. The Morris water maze (MWM) test was used to determine spatial learning and memory performance. We assessed the effect of repeated sevoflurane exposure on histone acetylation and the expression of brain-derived neurotropic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), in the hippocampus by Western blot (WB). To detect neurogenesis, we first counted the number of neural stem cells (NSCs); we then assessed their proliferation level by immunohistochemistry and estimated the number of new-born cells by immunofluorescence. We found that sevoflurane induced learning and memory deficits in young mice 4 weeks after sevoflurane exposure and that NaB injection restored histone acetylation and improved the performance of the mice in the MWM. NaB also increased the number and proliferation of NSCs and neonatal cells, which were inhibited by sevoflurane. Concomitantly, BDNF and TrkB expression, which was decreased by sevoflurane, was also restored by NaB. Our study showed that sevoflurane affects long-term neurocognitive function and neurogenesis in young mice. Normalization of histone acetylation may alleviate the neurodevelopmental side effects of this anaesthetic.
在过去十年中，吸入麻醉剂暴露会抑制神经发生并导致记忆缺陷这一可能性引起了广泛关注。本研究旨在探讨七氟醚暴露诱导海马神经发生减少的机制。将幼鼠连续三天每天用3.0%七氟醚/60%氧气的气体混合物麻醉2小时。在麻醉前2小时开始给予丁酸钠（NaB），并持续每日给药直至行为测试结束。采用莫里斯水迷宫（MWM）试验来测定空间学习和记忆能力。我们通过蛋白质免疫印迹法（WB）评估反复七氟醚暴露对海马中组蛋白乙酰化、脑源性神经营养因子（BDNF）及其受体原肌球蛋白相关激酶受体B（TrkB）表达的影响。为了检测神经发生，我们首先计数神经干细胞（NSC）的数量；然后通过免疫组织化学评估其增殖水平，并通过免疫荧光估计新生细胞的数量。我们发现，七氟醚暴露4周后，幼鼠出现学习和记忆缺陷，而注射NaB可恢复组蛋白乙酰化，并改善小鼠在MWM中的表现。NaB还增加了NSC和新生细胞的数量及增殖，而这些在七氟醚作用下受到了抑制。同时，七氟醚降低的BDNF和TrkB表达也通过NaB得以恢复。我们的研究表明，七氟醚会影响幼鼠的长期神经认知功能和神经发生。组蛋白乙酰化的正常化可能会减轻这种麻醉剂的神经发育副作用。
