Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight

Nadia Houerbi, JangKeun Kim, Eliah G. Overbey, Richa Batra, Annalise Schweickart, Laura Patras, Serena Lucotti, Krista A. Ryon, Deena Najjar, Cem Meydan, Namita Damle, Christopher Chin, S. Anand Narayanan, Joseph W. Guarnieri, Gabrielle Widjaja, Afshin Beheshti, Gabriel Tobias, Fanny Vatter, Jeremy Wain Hirschberg, Ashley Kleinman, Evan E. Afshin, Matthew MacKay, Qiuying Chen, Dawson Miller, Aaron S. Gajadhar, Lucy Williamson, Purvi Tandel, Qiu Yang, Jessica Chu, Ryan Benz, Asim Siddiqui, Daniel Hornburg, Steven Gross, Bader Shirah, Jan Krumsiek, Jaime Mateus, Xiao Mao, Irina Matei () and Christopher E. Mason ()
Additional contact information
Nadia Houerbi: Weill Cornell Medicine
JangKeun Kim: Weill Cornell Medicine
Eliah G. Overbey: Weill Cornell Medicine
Richa Batra: Weill Cornell Medicine
Annalise Schweickart: Weill Cornell Medicine
Laura Patras: Weill Cornell Medicine
Serena Lucotti: Weill Cornell Medicine
Krista A. Ryon: Weill Cornell Medicine
Deena Najjar: Weill Cornell Medicine
Cem Meydan: Weill Cornell Medicine
Namita Damle: Weill Cornell Medicine
Christopher Chin: Weill Cornell Medicine
S. Anand Narayanan: Florida State University
Joseph W. Guarnieri: Children’s Hospital of Philadelphia
Gabrielle Widjaja: Children’s Hospital of Philadelphia
Afshin Beheshti: Broad Institute of MIT and Harvard
Gabriel Tobias: Weill Cornell Medicine
Fanny Vatter: Weill Cornell Medicine
Jeremy Wain Hirschberg: Weill Cornell Medicine
Ashley Kleinman: Weill Cornell Medicine
Evan E. Afshin: Weill Cornell Medicine
Matthew MacKay: Weill Cornell Medicine
Qiuying Chen: Weill Cornell Medicine
Dawson Miller: Weill Cornell Medicine
Aaron S. Gajadhar: Inc.
Lucy Williamson: Inc.
Purvi Tandel: Inc.
Qiu Yang: Inc.
Jessica Chu: Inc.
Ryan Benz: Inc.
Asim Siddiqui: Inc.
Daniel Hornburg: Inc.
Steven Gross: Weill Cornell Medicine
Bader Shirah: King Faisal Specialist Hospital & Research Centre
Jan Krumsiek: Weill Cornell Medicine
Jaime Mateus: Space Exploration Technologies Corporation (SpaceX)
Xiao Mao: Loma Linda University Health
Irina Matei: Weill Cornell Medicine
Christopher E. Mason: Weill Cornell Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48841-w

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