Effects of Low Dose Space Radiation Exposures on the Splenic Metabolome

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.

Mitochondrial Effects in the Liver of C57BL/6 Mice by Low Dose, High Energy, High Charge Irradiation

“…Laiakis et al [ 52 ] recently proposed HZE-induced mitochondrial dysfunction based on HZE-induced metabolite changes in mouse spleen. Mitochondrial stress was also recently proposed in a comprehensive multi-omics analysis from 59 astronauts and hundreds of samples that have been on space missions [ 53 ].…”

Stem Cell Therapy for Sequestration of Traumatic Brain Injury-Induced Inflammation

“…Each deep spaceflight stressor, or a combination thereof, may represent unique circulating immune responses coupled with an altered immune system, as evidenced by circulating plasma microRNA sequence analysis [ 48 ]. Space radiation-induced dysregulated brain inflammation is also reflected in the spleen [ 40 , 49 ], suggesting a robust and whole-body alteration in immune response, which resembles the TBI signature of brain and splenic inflammation [ 50 , 51 , 52 ]. While still scarce, these reports suggest that radiation-exposed individuals (from uncontrolled sources, therapeutic intervention and space exploration) may be vulnerable to upregulated central and peripheral inflammation, warranting their careful monitoring for TBI-like symptoms and treatment.…”

Editorial to the Special Issue: “Dysregulation of Human Molecular and Metabolic Mechanisms Resulting in Oxidative Stress and Damage Generation in the Space Environment”

“…Indeed, contributions to this syndrome may stem from concomitant hyper-exposure to several toxic factors, including the explicitly increased high energy radiation, reduced gravity or microgravity (μG), hypoxia and hyperoxia conditions observed in each and every extravehicular activity (EVA), and the inevitable inhalation of Moon and Mars dust and/or regolith attendant to prolonged planetary exploration [ 4 , 5 , 6 , 7 ]. These first two factors (radiation and μG) continue to be routinely investigated and considerable data have been accumulated in the popular and scientific literature, reflecting the impact on the OSaD coefficient via genomic, proteomic, and metabolomic responses [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. However, variances in gas content and pressures, and the induction of potentially toxic dust/regolith particles into the physiology has to date not been interrogated significantly in the research literature, especially in the context of the combinatorial threat of all these major factors impacting the physiology simultaneously.…”

“…To address multiple OSaD factors in chorus with one another, the choice of research model is critical and certainly the likelihood that multiple models may need to be employed is warranted. The current scientific literature documents have extensively employed rodent and human physiological platforms to evaluate OSaD generated toxic effects, spanning many different physiological and analytical subsystem models [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”