Exposure to sevoflurane and other inhalational anesthetics can induce cognitive impairment in elderly patients. Studies have indicated that methylene blue (MB) has beneficial effects on multiple neurodegenerative diseases and the mechanism involves mitochondrial function preservation. However, whether MB can attenuate the cognitive decline induced by sevoflurane in aged mice requires further investigation. Forty-five 18-month-old C57/BL mice were used to establish a model of sevoflurane-induced cognitive impairment in which the mice were exposed to 3% sevoflurane for 2 h. Mice in the MB group were intraperitoneally injected with MB at a dose of 5 mg/kg before sevoflurane inhalation. The Morris water maze test was used to evaluate the learning and memory performances. We also examined changes in mitochondrial morphology as well as the expression and interaction of related proteins in the aged hippocampus. Parkin, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), mitochondrial dynamin-related protein 1 (Drp1), small ubiquitin-like modifier (SUMO2/3), SUMO-specific proteases 3 (SENP3), and ubiquitin-like conjugating enzyme 9 expression in the mouse hippocampus was detected by western blotting, and SUMO2/3-Drp1 was examined by coimmunoprecipitation. Exposure to sevoflurane increased SENP3 expression and Drp1 deSUMOylation in the aged hippocampus and resulted in cognitive deficiency. MB attenuated sevoflurane-induced memory loss and mitochondrial fragmentation and decreased Drp1 deSUMOylation in the aged hippocampus. This neuroprotective effect provides a mechanistic explanation for how the SUMOylation status of Drp1 acts as a key switch in the cognitive dysfunction induced by sevoflurane.

中文翻译：

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亚甲蓝通过抑制年老小鼠的Drp1 deSUMOylation来防止七氟醚引起的认知功能障碍。

暴露于七氟醚和其他吸入麻醉药可导致老年患者认知障碍。研究表明，亚甲基蓝（MB）对多种神经退行性疾病具有有益作用，其机制涉及线粒体功能的保存。但是，MB是否能减轻七氟醚在衰老小鼠中引起的认知能力下降，尚需进一步研究。45只18个月大的C57 / BL小鼠用于建立七氟醚诱发的认知障碍模型，其中将小鼠暴露于3％的七氟醚2 h。在吸入七氟醚之前，向MB组的小鼠腹膜内注射5 mg / kg的MB。莫里斯水迷宫测试用于评估学习和记忆表现。我们还检查了老年海马中线粒体形态的变化以及相关蛋白的表达和相互作用。Parkin，BCL2 /腺病毒E1B 19 kDa蛋白相互作用蛋白3（BNIP3），线粒体动力蛋白相关蛋白1（Drp1），小泛素样修饰剂（SUMO2 / 3），SUMO特异性蛋白酶3（SENP3）和泛素-通过免疫印迹法检测小鼠海马中的共轭酶9样表达，并通过共免疫沉淀法检测SUMO2 / 3-Drp1。暴露于七氟醚中会增加老年海马中的SENP3表达和Drp1 deSUMOylation，并导致认知缺陷。在老年海马中，MB减弱了七氟醚引起的记忆丧失和线粒体片段化，并降低了Drp1 deSUMOylation。