A novel partial gravity ground-based analog for rats via quadrupedal unloading

Abstract

Musculoskeletal deconditioning is a well-known consequence of microgravity. However, the effects of partial gravity, such as that experienced on the moon (0.16 g) or Mars (0.38 g), on musculoskeletal health remain relatively unexplored. Because Mars is being increasingly viewed as the likely next extraterrestrial site for human exploration, there is an increasing need for Earth-based models that can replicate the long-term physiological effects of microgravity. These models would also offer the opportunity to explore the potential impact of partial artificial gravity (as would be achieved by centrifugation). In this study, we describe a novel partial gravity model that can be employed in rats over extended periods of time. We demonstrate that 2 wk of partial weight bearing at 20, 40, or 70% of normal loading affects the musculoskeletal health of the animals, as evidenced by decreased trabecular bone density (ranging from -7.5 ± 2.7% at 70% of normal loading to -27.9 ± 2.9% at 20%), hindlimb muscle mass, and impaired muscle function as characterized by grip force. This new model will facilitate studies of the physiological changes occurring in partial gravity and allow for the design of potential countermeasures to mitigate these changes. NEW & NOTEWORTHY This research article describes the first quadrupedal unloading model in rats that is sustainable for investigating the physiological alterations occurring in partial gravity environments, providing a new and adaptable model for ground-based research for future space exploration.

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

“…However, reduced mechanical loading leads to a significant loss of rear paw grip force after 2 weeks. These results, while preliminary, are rather different than what was observed in our previous studies with males, where we highlighted that hindlimb grip force decreases by over 20% after 14 days of exposure to PWB40 (Mortreux et al, 2018(Mortreux et al, , 2019c. Previous research has shown that females' muscles are more resistant to fatigue compared to their male counterparts (Glenmark et al, 2004) and hindlimb unloading studies conducted on Wistar rats of both sexes also emphasized the differences in bone adaptation, where 14 days of hindlimb unloading led to a significant reduction in femoral bone mineral density in male, but not in female Wistar rats (David et al, 2006).…”

“…In this pilot study, we demonstrate the first use of a PWB model for adult female rats, at one level of partial unloading (40%) for 14 consecutive days compared to fully loaded animals. 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.…”

“…Fourteen Wistar female rats (Charles River Laboratories, Wilmington, MA, United States) weighing 282.96 ± 5.43 g (14 week of age) were obtained and housed in a temperaturecontrolled facility (22 ± 2 • C) under a 12:12 h light-dark cycle (lights on starting at 7:00 am) with water and regular chow provided ad libitum. Rats were allowed to acclimate to their single housing for 48 h before being exposed to different levels of PWB for 14 days according to our previously described protocol (Mortreux et al, 2018). 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).…”

“…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).…”