Oral antioxidant edaravone protects against cognitive deficits induced by chronic hypobaric hypoxia at high altitudes.

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-03 DOI:10.1038/s41398-024-03133-1
Yuan-Yuan Ma, Xin Li, Zhong-Yuan Yu, Tong Luo, Cheng-Rong Tan, Yu-Di Bai, Gang Xu, Bin-Da Sun, Xian-Le Bu, Yu-Hui Liu, Wang-Sheng Jin, Yu-Qi Gao, Xin-Fu Zhou, Juan Liu, Yan-Jiang Wang
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Abstract

Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas.

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口服抗氧化剂依达拉奉可防止高海拔地区长期低压缺氧引起的认知障碍。
高海拔地区的长期低压缺氧会损害认知功能,尤其是造成学习和记忆障碍,需要进行治疗干预。在这里,我们发现小鼠在一个月的低压缺氧(模拟海拔 5000 米)环境中会出现明显的认知功能障碍,同时大脑和血液中的氧化应激生物标志物水平也会升高。依达拉奉是一种被批准用于治疗缺血性中风和肌萎缩性脊髓侧索硬化症的自由基清除剂,口服依达拉奉的新型制剂可显著缓解氧化应激和慢性低压缺氧引起的认知障碍。此外,口服依达拉奉还能减轻神经炎症,恢复海马神经干细胞的衰竭。此外,骨膜蛋白(Postn)在慢性低压缺氧导致的认知障碍中起着至关重要的作用,可能是依达拉奉的一个分子靶点。总之,我们的研究结果表明,氧化应激在慢性低压缺氧导致的认知障碍中起着至关重要的作用,而口服依达拉奉是防止高海拔地区慢性低压缺氧导致的认知障碍的一种潜在药物。
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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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