Longitudinal time course of muscle impairments during partial weight-bearing in rats

Abstract

In the near future, space agencies plan to send the first crews for extended stays on the Moon and Mars, where gravity is significantly reduced compared to Earth (0.16× g and 0.38× g , respectively). However, the long-term effects of partial gravity have not yet been elucidated, and ensuring astronauts’ health and performance is crucial to the success of these missions. Using a quadrupedal partial weight-bearing (PWB) model in rats that we designed, we investigated the longitudinal time course of muscle function at three different PWB levels. We demonstrated that both muscle mass and muscle function are significantly impaired in reduced weight-bearing environments as early as after 7 days of suspension. Moreover, we showed that muscular alterations are correlated to the PWB level and do not reach a plateau during a 1-month exposure to reduced weight-bearing, emphasizing the need for mitigating countermeasures for safe and successful extraterrestrial exploration.

Partial Weight-Bearing in Female Rats: Proof of Concept in a Martian-Gravity Analog

“…Similarly to our previous observations of PWB in male rats (Mortreux et al, 2018), we showed that the PWB system is extremely steady and reliable over time with a coefficient of variation (CoV) of 2.1% during the 2-week experiment. Despite being greater than the 1.2% CoV value in male animals previously reported by our group for periods of 2 to 4 weeks (Mortreux et al, 2019a), the CoV reported here remains well below our target range of ±5%.…”

“…Overall, females appear to tolerate well the period of partial mechanical unloading. While PWB led to a transient body weight loss in male rats (Mortreux et al, 2018(Mortreux et al, , 2019a,c), we did not observe any significant fluctuations of the females' body weight, either compared to the control group or to their pre-suspension baseline. This sex-based difference has been reported previously after exposure to 14 and 30 days of hindlimb unloading (Il'ina-Kakueva, 2002;David et al, 2006;Chang et al, 2018;Deschenes et al, 2018), and in our study, was further associated with a similar food intake, which was eventually greater at the end of the experiment in the PWB40 group when normalized to animals' body weight, compared to the PWB100 controls.…”

“…Interestingly, our terminal assessments of several muscles revealed that muscle and myofiber size seemed differently impacted in female rats compared to those observed in male rats in the same conditions. In the hindlimbs, the postural soleus muscle is usually the first impacted by total and mechanical unloading (Fitts et al, 2000(Fitts et al, , 2001Mortreux et al, 2019a), where it is associated with a preferential decrease of type-I myofiber size (Ploutz-Snyder et al, 2014;Baehr et al, 2017) and a typical myofiber switch from type I (slow) to type II (fast) fibers (McDonald et al, 1994;Desplanches, 1997;Shenkman, 2016;Mortreux et al, 2019b).…”

“…On day 0 (baseline), each rat was placed into one of two conditions, to ensure equal distribution of the body weights across the groups: normal loading with full harness (PWB100) and 40% of normal loading (PWB40). Achieved PWB level was calculated daily by recording the fully loaded weight and the unloaded weight on a digital animal scale as previously described (Mortreux et al, 2019a), and the chain length was adjusted in case of a deviation greater than 5% of the desired PWB level. All experiments were performed during the light-phase.…”

“…Similarly, ground-based models, which are crucial in order to better understand the muscle deconditioning that occurs in space, have had a strong male bias, and rare studies have used hindlimb unloading in adult females (Peres-Ueno et al, 2017). Our recently developed rat partial weight-bearing (PWB) analog has proven to be a reliable (Mortreux et al, 2018) and consistent (Mortreux et al, 2019a) model, and when combined with the hindlimb suspension via pelvic harness (HLS), can be used to represent an additional period in microgravity (Mortreux et al, 2019c), mimicking a trip to and from these extraterrestrial bodies. However, this PWB model has only been used in adult male rats thus far (Mortreux et al, 2019b).…”