Early Adaptation To Increased Mechanical Loading After Disuse: Muscle Response In Male And Female Rats

Abstract

On top of musculoskeletal alterations during spaceflight, reloading upon return induces muscle deterioration and prolongs recovery. Astronauts will return to the lunar surface by 2024, and plan for a future landing on Mars, where they will experience gravity shifts. PURPOSE: To understand the impact of acute gravitational reloading following disuse in both sexes. METHODS: 141 Adult Wistar rats were unloaded for 14d to establish muscle deconditioning, and then exposed to either 4 h or 24 h or partial weight-bearing (PWB) at 20, 40, or 100% of normal loading to simulate early adaptation to the Moon, Mars, and Earth’s gravity, respectively. Muscle strength, function and composition were assessed. Gene expression was performed in the soleus muscle using RTqPCR. RESULTS: After 14d of unloading, males lost more weight and displayed a greater decline in grip strength than females (-53.7% vs -35.9%, p < 0.0001), which was associated with greater atrophy of the soleus (p = 0.009). After 4 h of reloading, males displayed increased grip force while females did not. After 24 h, only males reloaded at PWB100 and PWB20 had a significant increase in grip strength but no change in gastrocnemius mass. Soleus mass decreased in females but increased in all males. In the soleus, myofiber size was greater in reloaded animals compared to HLS, but more so in males reloaded at PWB40 (p = 0.0002). Compared to HLS animals, gastrocnemius, myofiber size was higher in reloaded males but identical in reloaded females, regardless of the PWB level. Interestingly, reloaded males showed an increased proportion of type 1 myofibers, while females displayed an increase in hybrid myofibers. Gene expression highlighted that males were able to significantly upregulate several genes involved in muscle regeneration, including Pax7, MyoD, MyoG, Ubr5, as early as after 4 hr of reloading, while females did not. CONCLUSION: Early adaptation to PWB after unloading results in a rapid increase in grip strength in males, but not in females. Moreover, the ability for males to induce gene expression immediately following reloading might contribute to the improve muscle function. Muscle composition during recovery seems to be plastic and sex-dependent, suggesting a complex set of influences on muscle recovery after disuse. This work was supported by NASA (80NSSC19K1598).