Loss of physical contact in space alters the dopamine system in C. elegans
Surabhi Sudevan,
Kasumi Muto,
Nahoko Higashitani,
Toko Hashizume,
Akira Higashibata,
Rebecca A. Ellwood,
Colleen S. Deane,
Mizanur Rahman,
Siva A. Vanapalli,
Timothy Etheridge,
Nathaniel J. Szewczyk,
Atsushi Higashitani
Affiliations
Surabhi Sudevan
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan; Medical Research Council (MRC) Versus Arthritis Centre for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, UK; Musculoskeletal Conditions, National Institute for Health Research Nottingham Biomedical Research Centre, Derby, UK
Kasumi Muto
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
Nahoko Higashitani
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
Human Spaceflight Technology Directorate, Japan Aerospace Exploration Agency, 2-1-1 Sengen, Tsukuba, Ibaraki 305-8505, Japan
Rebecca A. Ellwood
Medical Research Council (MRC) Versus Arthritis Centre for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, UK; Musculoskeletal Conditions, National Institute for Health Research Nottingham Biomedical Research Centre, Derby, UK
Colleen S. Deane
Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, St. Luke's Campus, Exeter, UK; Living Systems Institute, University of Exeter, StockerRoad, Exeter, UK
Mizanur Rahman
Department of Chemical Engineering, Texas Tech University, Lubbock, TX, USA
Siva A. Vanapalli
Department of Chemical Engineering, Texas Tech University, Lubbock, TX, USA
Timothy Etheridge
Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, St. Luke's Campus, Exeter, UK; Corresponding author
Nathaniel J. Szewczyk
Medical Research Council (MRC) Versus Arthritis Centre for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, UK; Musculoskeletal Conditions, National Institute for Health Research Nottingham Biomedical Research Centre, Derby, UK; Ohio Musculoskeletal and Neurologic Institute, Ohio University, Athens, OH, USA; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Corresponding author
Atsushi Higashitani
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan; Corresponding author
Summary: Progressive neuromuscular decline in microgravity is a prominent health concern preventing interplanetary human habitation. We establish functional dopamine-mediated impairments as a consistent feature across multiple spaceflight exposures and during simulated microgravity in C. elegans. Animals grown continuously in these conditions display reduced movement and body length. Loss of mechanical contact stimuli in microgravity elicits decreased endogenous dopamine and comt-4 (catechol-O-methyl transferase) expression levels. The application of exogenous dopamine reverses the movement and body length defects caused by simulated microgravity. In addition, increased physical contact made comt-4 and dopamine levels rise. It also increased muscular cytoplasmic Ca2+ firing. In dop-3 (D2-like receptor) mutants, neither decrease in movement nor in body length were observed during simulated microgravity growth. These results strongly suggest that targeting the dopamine system through manipulation of the external environment (contact stimuli) prevents muscular changes and is a realistic and viable treatment strategy to promote safe human deep-space travel.
