Abstract

Unloading‐induced atrophy and exposure to space radiation are considered major physiological limitations to future space exploration. Muscle mass and muscle strength loss have been reported in models of hindlimb unloading and have been associated with fiber type changes and a shift toward more glycolytic activity. It is commonly purported that skeletal muscle is radio‐resistant due to its post mitotic state, but recent work has indicated changes in both protein synthesis rates and muscle morphometry with exposure to high‐charge high energy particles. While unloading‐induced atrophy has been widely studied in models of complete unloading, information on muscle atrophy in partial loading conditions is much less common, but there is indication that muscle anabolism is linked to gravitational load or lack thereof. It is clear that space exploration includes both space radiation‐ and unloading‐induced atrophy; however, the combined effects of these two environmental factors has limited investigation. The purpose of this study was to determine the impact of acute radiation exposure, with or without the addition of partial loading on skeletal muscle anabolic signaling.METHODSBALB/cByJ (4mo female) mice were assigned either to full weight bearing or partial weight bearing equal to 1/6th bodyweight groups. These groups were then further divided into either single 0.5 Gy of 300 MeV whole–body 28 Si radiation exposure (GCR) or sham. Radiation exposure occurred on Day 0 at Brookhaven National Laboratory and was followed by 21d of Earth (1G) or Lunar (G/6) loading. Muscles of the hind limb were examined for common markers of protein anabolism. Protein expression was measured in the quadriceps using western blot techniques and fiber type was measured using immunohistochemistry.RESULTSOur data indicate that neither GCR exposure nor Lunar loading alone altered mTORC1 dependent signaling. DEPTOR expression was significantly lower when lunar loading and radiation were combined, which may be an indication of bolstered repair response (P<0.05). Interestingly, radiation exposure had higher phosphorylation of ERK1/2 when compared to SHAM counterparts (CC 3.2 fold increase, and 5.6 fold increase in G/6 groups), and was associated with the preservation of muscle mass and the predominance of type 2 fiber composition in the irradiated animals of this experiment.CONCLUSIONThis study suggests that heavy ion exposure affects skeletal muscle and can lead to discrete and combined effects in anabolic signaling.Support or Funding InformationThis study was funded in part by National Space Biomedical Research Institute.

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