Musculoskeletal Changes in Mice from 20–50 cGy of Simulated Galactic Cosmic Rays

Abstract

On a mission to Mars, astronauts will be exposed to a complex mix of radiation from galactic cosmic rays. We have demonstrated a loss of bone mass from exposure to types of radiation relevant to space flight at doses of 1 and 2 Gy. The effects of space radiation on skeletal muscle, however, have not been investigated. To evaluate the effect of simulated galactic cosmic radiation on muscle fiber area and bone volume, we examined mice from a study in which brains were exposed to collimated iron-ion radiation. The collimator transmitted a complex mix of charged secondary particles to bone and muscle tissue that represented a low-fidelity simulation of the space radiation environment. Measured radiation doses of uncollimated secondary particles were 0.47 Gy at the proximal humerus, 0.24-0.31 Gy at the midbelly of the triceps brachii, and 0.18 Gy at the proximal tibia. Compared to nonirradiated controls, the proximal humerus of irradiated mice had a lower trabecular bone volume fraction, lower trabecular thickness, greater cortical porosity, and lower polar moment of inertia. The tibia showed no differences in any bone parameter. The triceps brachii of irradiated mice had fewer small-diameter fibers and more fibers containing central nuclei. These results demonstrate a negative effect on the skeletal muscle and bone systems of simulated galactic cosmic rays at a dose and LET range relevant to a Mars exploration mission. The presence of evidence of muscle remodeling highlights the need for further study.

The effect of radiation dose on mouse skeletal muscle remodeling

“…Radiation to the hindlimbs was performed as previously described, with slight modifications 27. Animals were anesthetized with 4% isoflurane and placed in an irradiator device (X-RAD 320, North Branford, CT).…”

“…However, fractionating radiation into smaller doses attenuates skeletal muscle amino acid release when compared to a single larger dose 25. Despite the potential benefits of fractionation, lower radiation doses that are more clinically relevant can also impair skeletal muscle development26 and increase indices of muscle remodeling 27. Altered muscle plasticity following radiation exposure has been attributed to impaired satellite cell activity 26,28,29.…”

Influence of longitudinal radiation exposure from microcomputed tomography scanning on skeletal muscle function and metabolic activity in female CD-1 mice

“…However, some studies have examined low‐dose radiation (<30 cGy) exposure on rodent skeletal muscle, using sources other than X‐rays, including 56 Fe (Bandstra et al. 2009; Shtifman et al. 2013) and γ (Masuda et al.…”

“…Similarly, a single low‐dose (15–31 cGy) whole body 56 Fe radiation caused increased centralized nuclei (surrogate measure of muscle regeneration) and decreased fiber cross‐sectional area of triceps brachii 9 weeks postexposure (Bandstra et al. 2009) and flexor digitorum brevis 7 days postexposure (Shtifman et al. 2013).…”

Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

“…There is evidence that IR above 1 Gy could induce osteopenia, which might be due to an increase of osteoclasts and bone resorption, as a consequence of changes in osteoprogenitors (Kondo et al, 2009, 2010; Willey et al, 2010; Yumoto et al, 2010). In mice, even ≤0.5 Gy of heavy ion exposure can induce osteopenia (Bandstra et al, 2009; Yumoto et al, 2010), which indicates that space radiation can stimulate microgravity-induced osteopenia; although, it remains unclear whether space radiation-induced osteopenia has a synergistic or additive effect (Alwood et al, 2010; Lloyd et al, 2012). Therefore, it is important to elucidate the mechanism by which radiation and microgravity promote osteopenia.…”