Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice

Yuvarani Masarapu, Egle Cekanaviciute, Zaneta Andrusivova, Jakub O. Westholm, Åsa Björklund, Robin Fallegger, Pau Badia-i-Mompel, Valery Boyko, Shubha Vasisht, Amanda Saravia-Butler, Samrawit Gebre, Enikő Lázár, Marta Graziano, Solène Frapard, Robert G. Hinshaw, Olaf Bergmann, Deanne M. Taylor, Douglas C. Wallace, Christer Sylvén, Konstantinos Meletis, Julio Saez-Rodriguez, Jonathan M. Galazka, Sylvain V. Costes () and Stefania Giacomello ()
Additional contact information
Yuvarani Masarapu: KTH Royal Institute of Technology
Egle Cekanaviciute: NASA Ames Research Center
Zaneta Andrusivova: KTH Royal Institute of Technology
Jakub O. Westholm: Science for Life Laboratory
Åsa Björklund: Uppsala University
Robin Fallegger: Bioquant
Pau Badia-i-Mompel: Bioquant
Valery Boyko: NASA Ames Research Center
Shubha Vasisht: The Children’s Hospital of Philadelphia Research Institute
Amanda Saravia-Butler: NASA Ames Research Center
Samrawit Gebre: NASA Ames Research Center
Enikő Lázár: KTH Royal Institute of Technology
Marta Graziano: Biomedicum
Solène Frapard: KTH Royal Institute of Technology
Robert G. Hinshaw: NASA Ames Research Center
Olaf Bergmann: Karolinska Institute
Deanne M. Taylor: The Children’s Hospital of Philadelphia Research Institute
Douglas C. Wallace: The University of Pennsylvania Perelman School of Medicine
Christer Sylvén: Karolinska Institute
Konstantinos Meletis: Biomedicum
Julio Saez-Rodriguez: Bioquant
Jonathan M. Galazka: NASA Ames Research Center
Sylvain V. Costes: NASA Ames Research Center
Stefania Giacomello: KTH Royal Institute of Technology

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).

Date: 2024
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DOI: 10.1038/s41467-024-48916-8

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