Tandem mass tag-based quantitative proteomic analysis of effects of multiple sevoflurane exposures on the cerebral cortex of neonatal and adult mice.
Tandem mass tag-based quantitative proteomic analysis of effects of multiple sevoflurane exposures on the cerebral cortex of neonatal and adult mice.
复制标题
多次七氟醚暴露对新生和成年小鼠大脑皮层影响的串联质量标记定量蛋白质组学分析。
DOI：
10.3389/fneur.2022.1056947
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发表时间：
2022
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
七氟烷是儿科手术中最常用的全身麻醉剂，但其具有潜在的神经毒性。先前的研究发现，长期或多次七氟烷暴露可能导致新生小鼠而不是成年小鼠的认知缺陷，而短期或单次吸入对两个年龄段的认知功能几乎没有影响。然而，这些影响背后的机制尚不清楚。在本研究中，七氟醚组中6天和60日龄的C57 bl小鼠连续3天给予3%七氟醚加60%氧气，每次持续2小时，而对照组仅给予60%氧气。在第8天或第62天收获皮质组织。采用基于TMT pro的定量蛋白质组学技术，结合液相色谱-串联质谱（LC-MS/MS）分析、高尔基体染色和蛋白质印迹分析，研究了不同年龄段小鼠多次七氟醚麻醉对大脑皮层的影响。在对照或多次七氟烷给药后，从出生后第30天（P）至P36或P84至P90进行Morris水迷宫（MWM）试验。七氟烷麻醉影响空间学习和记忆，并主要在新生小鼠中减少树突棘，而成熟动物没有表现出显着的变化。使用TMTpro标记和LC-MS/MS联合定量蛋白质组学方法测量了总共6247种蛋白质，其中443种与重复七氟烷麻醉的年龄依赖性神经毒性机制相关。此外，蛋白质印迹研究表明，七氟烷诱导的新生小鼠脑损伤可能是通过增加CHGB、PTEN、MAP 2c蛋白表达水平或降低SOD 2蛋白表达水平介导的。本研究结果将有助于进一步研究年龄依赖性麻醉神经毒性的机制，并有助于寻求在全身麻醉下对发育中的大脑的有效保护。
Sevoflurane is the most commonly used general anesthetic in pediatric surgery, but it has the potential to be neurotoxic. Previous research found that long-term or multiple sevoflurane exposures could cause cognitive deficits in newborn mice but not adult mice, whereas short-term or single inhalations had little effect on cognitive function at both ages. The mechanisms behind these effects, however, are unclear. In the current study, 6- and 60-day-old C57bl mice in the sevoflurane groups were given 3% sevoflurane plus 60% oxygen for three consecutive days, each lasting 2 hours, while those in the control group only got 60% oxygen. The cortex tissues were harvested on the 8th or 62nd day. The tandem mass tags (TMT)pro-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, Golgi staining, and western blotting analysis were applied to analyze the influences of multiple sevoflurane anesthesia on the cerebral cortex in mice with various ages. The Morris water maze (MWM) test was performed from postnatal day (P)30 to P36 or P84 to P90 after control or multiple sevoflurane treatment. Sevoflurane anesthesia affected spatial learning and memory and diminished dendritic spines primarily in newborn mice, whereas mature animals exhibited no significant alterations. A total of 6247 proteins were measured using the combined quantitative proteomics methods of TMTpro-labeled and LC-MS/MS, 443 of which were associated to the age-dependent neurotoxic mechanism of repeated sevoflurane anesthesia. Furthermore, western blotting research revealed that sevoflurane-induced brain damage in newborn mice may be mediated by increasing the levels of protein expression of CHGB, PTEN, MAP2c, or decreasing the level of SOD2 protein expression. Our findings would help to further the mechanistic study of age-dependent anesthetic neurotoxicity and contribute to seek for effective protection in the developing brain under general anesthesia.
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DOI：
10.1523/jneurosci.0295-20.2020
发表时间：
2021-01-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fracassi A;Marcatti M;Zolochevska O;Tabor N;Woltjer R;Moreno S;Taglialatela G
通讯作者：
Taglialatela G
影响因子：
9
作者：
Park, Tae-Jun;Park, Jei Hyoung;Lee, Sang Chul
通讯作者：
Lee, Sang Chul
影响因子：
1.8
作者：
Yang, Man;Tan, Hong;Yu, Yonghao
通讯作者：
Yu, Yonghao
影响因子：
2.4
作者：
Shin JG;Kim JH;Park CS;Kim BJ;Kim JW;Choi IG;Hwang J;Shin HD;Woo SI
通讯作者：
Woo SI
影响因子：
4.8
作者：
Li X;Wu Z;Zhang Y;Xu Y;Han G;Zhao P
通讯作者：
Zhao P