Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight
Nadia Houerbi, JangKeun Kim, Eliah Overbey, Richa Batra, Annalise Schweickart, Laura Pătraș, Serena Lucotti, Krista Ryon, Deena Najjar, Cem Meydan, Namita Damle, Christopher R. Chin, S Narayanan, Joseph W. Guarnieri, Gabrielle A. Widjaja, Afshin Beheshti, Gabriel Cardial Tobias, Fanny A. Pelissier Vatter, Jeremy Wain Hirschberg, Ashley S. Kleinman, Evan E. Afshin, Matthew MacKay, Qiuying Chen, Dawson Miller, Aaron S. Gajadhar, Lucy Williamson, Purvi Tandel, Yang Qiu, Jessica Chu, Ryan W. Benz, Asim Siddiqui, Daniel Hornburg, Steven Gross, Bader Shirah, Jan Krumsiek, Jaime Mateus, Xiao Wen Mao, Irina Matei, Christopher E. Mason
Abstract
As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.