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

Authors

Affiliations

Yuvarani Masarapu

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Egle Cekanaviciute

Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA

Zaneta Andrusivova

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Jakub O. Westholm

National Bioinformatics Infrastructure Sweden, Department of Biochemistry and Biophysics, Stockholm University, Science for Life, SE

Åsa Björklund

Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, SE

Robin Fallegger

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquan, DE

Pau Badia-i-Mompel

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquan, DE

Valery Boyko

Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA

Bionetics, Yorktown, VA, USA

Shubha Vasisht

Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA, U, US

Amanda Saravia-Butler

KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA

Samrawit Gebre

Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA

Enikö Lázár

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden

Marta Graziano

Department of Neuroscience, Karolinska Institutet, Biomedicum, Solna, Sweden

Solene Frapard

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Robert G. Hinshaw

NASA Postdoctoral Program - Oak Ridge Associated Universities, NASA Ames Research Center, Moffett Field, CA, USA

Olaf Bergmann

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden

Deanne M Taylor

Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA, U, US

Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

Douglas C. Wallace

Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

Christer Sylven

Department of Medicine, Karolinska Institute, Huddinge, Sweden

Konstantinos Meletis

Department of Neuroscience, Karolinska Institutet, Biomedicum, Solna, Sweden

Julio Saez-Rodriguez

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquan, DE

Jonathan M. Galazka

Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA

Sylvain V. Costes

Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA

Stefania Giacomello

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

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).