Microgravity and radiation are stressors unique to the spaceflight environment that can have an impact on the central nervous system (CNS). These stressors could potentially lead to significant health risks to astronauts, both acutely during the course of a mission or chronically, leading to long-term, post-mission decrements in quality of life. The CNS is sensitive to oxidative injury due to high concentrations of oxidizable, unsaturated lipids and low levels of antioxidant defenses. The purpose of this study was to evaluate oxidative damage in the brain cortex and hippocampus in a ground-based model for spaceflight, which includes prolonged unloading and low-dose radiation. Whole-body low-dose/low-dose-rate (LDR) gamma radiation using 57Co plates (0.04 Gy at 0.01 cGy/h) was delivered to 6 months old, mature, female C57BL/6 mice (n = 4–6/group) to simulate the radiation component. Anti-orthostatic tail suspension was used to model the unloading, fluid shift and physiological stress aspects of the microgravity component. Mice were hindlimb suspended and/or irradiated for 21 days. Brains were isolated 7 days or 9 months after irradiation and hindlimb unloading (HLU) for characterization of oxidative stress markers and microvessel changes. The level of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation, was significantly elevated in the cortex and hippocampus after LDR + HLU compared to controls (P < 0.05). The combination group also had the highest level of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression compared to controls (P < 0.05). There was a significant decrease in superoxide dismutase (SOD) expression in the animals that received HLU only or combined LDR + HLU compared to control (P < 0.05). In addition, 9 months after LDR and HLU exposure, microvessel densities were the lowest in the combination group, compared to age-matched controls in the cortex (P < 0.05). Our data provide the first evidence that prolonged exposure to simulated microgravity and LDR radiation is associated with increased oxidative stress biomarkers that may increase the likelihood of brain injury and reduced antioxidant defense. NOX2-containing nicotinamide adenosine dinucleotide phosphate (NADPH oxidase) may contribute to spaceflight environment-induced oxidative stress.
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1 June 2016
Research Article|
May 31 2016
Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain
Xiao Wen Mao
;
Xiao Wen Mao
1
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
1Address for correspondence: Chan Shun Pavilion, Room A1018, 11175 Campus Street, Loma Linda University, Loma Linda, CA 92354; email: xmao@llu.edu.
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Nina C. Nishiyama
;
Nina C. Nishiyama
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
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Michael J. Pecaut
;
Michael J. Pecaut
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
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Mary Campbell-Beachler
;
Mary Campbell-Beachler
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
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Peter Gifford
;
Peter Gifford
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
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Kristine E. Haynes
;
Kristine E. Haynes
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
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Caroline Becronis
;
Caroline Becronis
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
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Daila S. Gridley
Daila S. Gridley
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, California 92354
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Radiat Res (2016) 185 (6): 647–657.
Article history
Received:
September 16 2015
Accepted:
April 04 2016
Citation
Xiao Wen Mao, Nina C. Nishiyama, Michael J. Pecaut, Mary Campbell-Beachler, Peter Gifford, Kristine E. Haynes, Caroline Becronis, Daila S. Gridley; Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain. Radiat Res 1 June 2016; 185 (6): 647–657. doi: https://doi.org/10.1667/RR14267.1
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