Effects of Low Dose Space Radiation Exposures on the Splenic Metabolome.

Evagelia C Laiakis,Igor Shuryak,Albert J Fornace,Brooke L Barnette,Yongjia Yu,Robert L Ullrich,Yi-Wen Wang,Mark R Emmett,Annabella Deziel

doi:10.3390/ijms22063070

Abstract

Future space missions will include a return to the Moon and long duration deep space roundtrip missions to Mars. Leaving the protection that Low Earth Orbit provides will unavoidably expose astronauts to higher cumulative doses of space radiation, in addition to other stressors, e.g., microgravity. Immune regulation is known to be impacted by both radiation and spaceflight and it remains to be seen whether prolonged effects that will be encountered in deep space can have an adverse impact on health. In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays, 16O, and 56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.

Highlights

Long duration and deep space travel are in the immediate National Aeronautics and Space Administration (NASA) plans for space exploration and research
We investigated the responses of low dose HZE and γ ray whole body exposures on whole spleen tissue metabolism in a longitudinal manner with doses that would be accumulated during a long duration mission and defined responses in select pathways, such as energy and purine metabolism
Purine metabolism is an important pathway for DNA and RNA synthesis, in addition to DNA repair and the generation of molecules that are critical components of nucleotides and cofactors [43]

Summary

Introduction

Long duration and deep space travel are in the immediate National Aeronautics and Space Administration (NASA) plans for space exploration and research. The space environment includes prolonged presence in microgravity, which on its own can lead to significant physiological changes [1,2], and exposures to space radiation, such as high energy (HZE) particles from galactic cosmic rays (GCRs) and potential particles from solar events (SPE) [3]. From astronaut health evaluations and animal experiments, both in space and on the ground, it is known that spaceflight and/or space radiation exposure have the potential to lead to significant effects such as cardiovascular and central nervous system effects, muscle atrophy, cataract formation, and, importantly, immune system effects, among others [1,4,5,6,7,8,9,10,11,12,13]. During a long duration mission, such physiological effects may prove detrimental to the completion of the tasks at hand and leave astronauts experiencing long-term health effects, as exposure to space radiation remains a significant risk. Substantial research efforts have been undertaken to understand the space flight environment and, in particular, the effects of the individual HZE particles and other types of space radiation on cellular and tissue responses

Methods

Results

Conclusion