Nogo-A Protein Mediates Oxidative Stress and Synaptic Damage Induced by High-Altitude Hypoxia in the Rat Hippocampus  

作　　者：Jinyu Fang Huaicun Liu Yanfei Zhang Quancheng Cheng Ziyuan Wang Xuan Fang Huiru Ding Weiguang Zhang Chunhua Chen 

机构地区：[1]Department of Human Anatomy and Histology and Embryology,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China

出　　处：《Biomedical and Environmental Sciences》2025年第1期79-93,共15页生物医学与环境科学(英文版)

基　　金：supported by Beijing Natural Science Foundation(No.7232090);the National Natural Science Foundation of China(82101306);the Scientific and Technological Innovation 2030(2021ZD0201100).

摘　　要：Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory.Nogo-A is an important axonal growth inhibitory factor.However,its function in high-altitude hypoxia and its mechanism of action remain unclear.Methods In an in vivo study,a low-pressure oxygen chamber was used to simulate high-altitude hypoxia,and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway.Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats,and synaptic damage in the hippocampus and changes in oxidative stress levels were observed.In vitro,SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion(OGD/R)models.Results Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats,triggered oxidative stress in the hippocampal tissue,and reduced the dendritic spine density of hippocampal neurons.Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress,synaptic damage,and the learning and memory impairment induced by high-altitude exposure.Conclusion Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure.

关 键 词：NOGO-A NgR1 High-altitude hypoxia Learning and memory Oxidative stress 

分 类 号：R339.54[医药卫生—人体生理学]