Effects of concomitant hypoxia and simulated microgravity on skeletal muscle, liver, and lungs in a novel experimental mouse model

IF 3.1 2区物理与天体物理 Q1 ENGINEERING, AEROSPACE

Acta Astronautica Pub Date : 2025-04-06 DOI:10.1016/j.actaastro.2025.04.010

Saeed Ahmad Khan , Josemin Jose , Gopika Ramachandran , Mutasem Rawas-Qalaji , Anu Ranade , Asima Karim , Firdos Ahmad , Rizwan Qaisar

{"title":"Effects of concomitant hypoxia and simulated microgravity on skeletal muscle, liver, and lungs in a novel experimental mouse model","authors":"Saeed Ahmad Khan , Josemin Jose , Gopika Ramachandran , Mutasem Rawas-Qalaji , Anu Ranade , Asima Karim , Firdos Ahmad , Rizwan Qaisar","doi":"10.1016/j.actaastro.2025.04.010","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The hindlimb unloaded (HU) mouse is an established model of simulated microgravity with pathologies of various body organs. However, the relevant effects of concomitant hypoxia in HU mice are unknown. We have developed a novel mouse model of hypoxia and HU to better simulate spaceflight conditions. Here, we investigated the cytoarchitecture and gene expressions of skeletal muscle, lungs, and liver tissues in HU mice with hypoxia.</div></div><div><h3>Methods</h3><div>We divided male, 4-month-old male c57BL/6j mice into four groups, normoxic and hypoxic ground-based controls and normoxic and hypoxic HU mice. The hypoxic group was exposed to 15 % oxygen during the second week of HU. We investigated histology and gene expressions of markers of endoplasmic reticulum stress and necroptosis in skeletal muscle, lungs, and liver tissues.</div></div><div><h3>Results</h3><div>The HU-hypoxic mice exhibited myofibers atrophy, maintenance of myonuclei count, and reduced myonuclear domain sizes compared to normoxic ground-based and HU mice (all p < 0.05). These mice also exhibited bronchial epithelial thinning and increased alveolar diameter (both p < 0.05). The liver tissues of HU-hypoxic mice exhibited higher hepatic fat content than ground-based normoxic mice. Lastly, we found elevated expressions of markers of endoplasmic reticulum stress and necroptosis in skeletal muscle, liver, and lung tissues.</div></div><div><h3>Conclusion</h3><div>Altogether, our results show that exposure to hypoxia worsens the histological injuries to skeletal muscle, lungs, and liver of HU mice. Further studies are required to characterize the negative effects of hypoxia and HU on various body organs.</div></div>","PeriodicalId":44971,"journal":{"name":"Acta Astronautica","volume":"232 ","pages":"Pages 580-587"},"PeriodicalIF":3.1000,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Astronautica","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0094576525002103","RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, AEROSPACE","Score":null,"Total":0}

引用次数: 0

Abstract

Background

The hindlimb unloaded (HU) mouse is an established model of simulated microgravity with pathologies of various body organs. However, the relevant effects of concomitant hypoxia in HU mice are unknown. We have developed a novel mouse model of hypoxia and HU to better simulate spaceflight conditions. Here, we investigated the cytoarchitecture and gene expressions of skeletal muscle, lungs, and liver tissues in HU mice with hypoxia.

Methods

We divided male, 4-month-old male c57BL/6j mice into four groups, normoxic and hypoxic ground-based controls and normoxic and hypoxic HU mice. The hypoxic group was exposed to 15 % oxygen during the second week of HU. We investigated histology and gene expressions of markers of endoplasmic reticulum stress and necroptosis in skeletal muscle, lungs, and liver tissues.

Results

The HU-hypoxic mice exhibited myofibers atrophy, maintenance of myonuclei count, and reduced myonuclear domain sizes compared to normoxic ground-based and HU mice (all p < 0.05). These mice also exhibited bronchial epithelial thinning and increased alveolar diameter (both p < 0.05). The liver tissues of HU-hypoxic mice exhibited higher hepatic fat content than ground-based normoxic mice. Lastly, we found elevated expressions of markers of endoplasmic reticulum stress and necroptosis in skeletal muscle, liver, and lung tissues.

Conclusion

Altogether, our results show that exposure to hypoxia worsens the histological injuries to skeletal muscle, lungs, and liver of HU mice. Further studies are required to characterize the negative effects of hypoxia and HU on various body organs.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Astronautica 工程技术-工程：宇航

CiteScore

7.20

自引率

22.90%

发文量

599

审稿时长

53 days

期刊介绍： Acta Astronautica is sponsored by the International Academy of Astronautics. Content is based on original contributions in all fields of basic, engineering, life and social space sciences and of space technology related to: The peaceful scientific exploration of space, Its exploitation for human welfare and progress, Conception, design, development and operation of space-borne and Earth-based systems, In addition to regular issues, the journal publishes selected proceedings of the annual International Astronautical Congress (IAC), transactions of the IAA and special issues on topics of current interest, such as microgravity, space station technology, geostationary orbits, and space economics. Other subject areas include satellite technology, space transportation and communications, space energy, power and propulsion, astrodynamics, extraterrestrial intelligence and Earth observations.