Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

Abstract

For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled with limited cargo areas, do not allow for large sample sizes onboard. In 1979, a model of hindlimb unloading (HU) was successfully created to mimic microgravity and has been used extensively since its creation. Four decades later, the first model of mouse partial weight-bearing (PWB) was developed, aiming at mimicking partial gravity environments. Return to the Lunar surface for astronauts is now imminent and prompted the need for an animal model closer to human physiology; hence in 2018, our laboratory created a new model of PWB for adult rats. In this review, we will focus on the rat model of PWB, from its conception to the current state of knowledge. Additionally, we will address how this new model, used in conjunction with HU, will help implement new paradigms allowing scientists to anticipate the physiological alterations and needs of astronauts. Finally, we will discuss the outstanding questions and future perspectives in space research and propose potential solutions using the rat PWB model.

Adaptation to full weight‐bearing following disuse in rats: The impact of biological sex on musculoskeletal recovery

“…Twenty‐one (Ingersoll et al., 2008 ) adult Wistar rats (10 males and 11 females) were obtained at 13 weeks of age (Charles River Laboratories, Wilmington, MA), and baseline assessments were performed 1 week later. Prior to baseline testing, animals were individually housed and placed in custom cages and allowed to acclimate for 24‐48 h. These cages, described elsewhere (Mortreux et al., 2018 ; Mortreux & Rosa‐Caldwell, 2020 ), are used to perform hindlimb suspension (HLS) and to house animals during full weight‐bearing recovery. Rats were placed in HLS for 14 days using a pelvic harness as previously described (Mortreux et al., 2019 , 2021 ), before being allowed to return to full weight‐bearing for 7 days.…”

Exploring the influence of microgravity on chemotherapeutic drug response in cancer: Unveiling new perspectives

“…74 F I G U R E 5 Schematic representation of (A) hindlimb unloading (B) tail suspension for rodent models. 28 Migration and metastasis of the cancer cells are majorly associated with the modulation of ECM components particularly Matrix metalloproteinases (MMPs) and TIMPs (Tissue inhibitors of metalloproteinase). [75][76][77] MMPs are majorly involved in the degradation of ECM and TIMPs play a crucial role in regulating ECM by MMPs, imbalance in these enzymes can significantly promote cancer metastasis.…”

“…In these models, the body of the animal makes an approximately 30° angle from the floor of the cage such that the animal does not touch the grid floor with its back feet 26,27 . This suspension ensures the removal of mechanical loading from the hindlimbs simulating microgravity conditions 28 …”

“… 26 , 27 This suspension ensures the removal of mechanical loading from the hindlimbs simulating microgravity conditions. 28 …”

Sex differences in muscle health in simulated micro- and partial-gravity environments in rats

“…Exposure to microgravity (or microgravity analogs) is well known to elicit musculoskeletal alterations in humans and in rodent models. 1 , 2 , 3 To mitigate these losses, NASA has instigated strict requirements for exercise interventions on the International Space Station (ISS). However, these interventions are time-consuming (∼2 ​h /day) and do not fully mitigate musculoskeletal losses.…”