Zhu Xiaozheng, Liu Huiping, Wang Diya, Guan Ruili, Zou Yuankang, Li Ming, Zhang Jianbin, Chen Jingyuan
Tianjin Institute of Environmental and Operational Medicine, China.
School of Medicine, Quzhou College of Technology, China.
Ecotoxicol Environ Saf. 2023 Apr 15;255:114828. doi: 10.1016/j.ecoenv.2023.114828. Epub 2023 Mar 28.
As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.
随着越来越多的人迁移到高海拔地区，高原脑病和缺氧诱导的认知障碍引起了公众的关注。然而，其潜在机制仍不清楚。新出现的证据表明，神经炎症和神经元丢失可能与之有关。在本研究中，我们调查了低氧损伤后小鼠的神经炎症和神经元丢失情况。我们的报告显示，低压缺氧暴露3周会导致小鼠空间探索和短期记忆受损，并伴有神经元丢失。此外，缺氧会诱导神经炎症和NLRP3炎性小体激活。此外，为了探究炎性小体在缺氧诱导的认知功能障碍中的作用，我们应用了NLRP3基因敲除小鼠，结果表明NLRP3可以负向调节GPX4以改变抗氧化能力。总之，我们的研究表明，缺氧暴露会导致神经炎症和神经元缺失，这可能是缺氧诱导认知障碍过程中的关键事件。NLRP3炎性小体通过负向调节GPX4促进抗氧化能力不足。
