Qin Zhao, Jinli Meng, Li Feng, Suyuan Wang, Kejin Xiang, Yonghong Huang, Hengyan Li, Xiaomei Li, Xin Hu, Lu Che, Yongxing Fu, Liming Zhao, Yunhong Wu, Wanlin He
{"title":"高海拔环境中的认知损伤机制:蛋白质组和代谢组的启示。","authors":"Qin Zhao, Jinli Meng, Li Feng, Suyuan Wang, Kejin Xiang, Yonghong Huang, Hengyan Li, Xiaomei Li, Xin Hu, Lu Che, Yongxing Fu, Liming Zhao, Yunhong Wu, Wanlin He","doi":"10.1021/acs.jproteome.4c00841","DOIUrl":null,"url":null,"abstract":"<p><p>High-altitude exposure can adversely affect neurocognitive functions; however, the underlying mechanisms remain elusive. Why and how does high-altitude exposure impair neurocognitive functions, particularly sleep? This study seeks to identify the molecular markers and mechanisms involved, with the goal of forming prevention and mitigation strategies for altitude sickness. Using serum proteomics and metabolomics, we analyzed blood samples from 23 Han Chinese plain dwellers before and after six months of high-altitude work in Tibet. The correlation analysis revealed biomarkers associated with cognitive alterations. Six months of high-altitude exposure significantly compromised cognitive function, notably, sleep quality. The key biomarkers implicated include SEPTIN5, PCBP1, STIM1, UBE2L3/I/N, amino acids (l/d-aspartic acid and l-glutamic acid), arachidonic acid, and S1P. Immune and neural signaling were suppressed, with sex-specific differences observed. This study innovatively identified GABA, arachidonic acid, l-glutamic acid, 2-arachidonoyl glycerol, and d-aspartic acid as biomarkers and elucidated the underlying mechanisms contributing to high-altitude-induced neurocognitive decline with a particular focus on sleep disruption. These findings pave the way for developing preventive measures and enhancing adaptation strategies. This study underscores the physiological significance of high-altitude adaptation, raising new questions about sex-specific responses and long-term consequences. 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Cognitive Impairment Mechanisms in High-Altitude Exposure: Proteomic and Metabolomic Insights.
High-altitude exposure can adversely affect neurocognitive functions; however, the underlying mechanisms remain elusive. Why and how does high-altitude exposure impair neurocognitive functions, particularly sleep? This study seeks to identify the molecular markers and mechanisms involved, with the goal of forming prevention and mitigation strategies for altitude sickness. Using serum proteomics and metabolomics, we analyzed blood samples from 23 Han Chinese plain dwellers before and after six months of high-altitude work in Tibet. The correlation analysis revealed biomarkers associated with cognitive alterations. Six months of high-altitude exposure significantly compromised cognitive function, notably, sleep quality. The key biomarkers implicated include SEPTIN5, PCBP1, STIM1, UBE2L3/I/N, amino acids (l/d-aspartic acid and l-glutamic acid), arachidonic acid, and S1P. Immune and neural signaling were suppressed, with sex-specific differences observed. This study innovatively identified GABA, arachidonic acid, l-glutamic acid, 2-arachidonoyl glycerol, and d-aspartic acid as biomarkers and elucidated the underlying mechanisms contributing to high-altitude-induced neurocognitive decline with a particular focus on sleep disruption. These findings pave the way for developing preventive measures and enhancing adaptation strategies. This study underscores the physiological significance of high-altitude adaptation, raising new questions about sex-specific responses and long-term consequences. It sets the stage for future research exploring individual variability and intervention efficacy.
期刊介绍:
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".