mimicking-space-mission-to-mars-using-hindlimb-unloading-partial

Mimicking a Space Mission to Mars Using Hindlimb Unloading and Partial Weight Bearing in Rats

Rodent ground-based models are widely used to understand the physiological consequences of space flight on the physiological system and have been ...

performing-vivo-ex-vivo-electrical-impedance-myography

Performing <em>In Vivo</em> and <em>Ex Vivo</em> Electrical Impedance Myography in Rodents

Electrical impedance myography (EIM) is a convenient technique that can be used in preclinical and clinical studies to assess muscle tissue health and ...

Harvard Medical School - Beth Israel Deaconess Medical Center

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.

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

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× and 0.38×, 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.

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

Many studies have investigated the physiological response to microgravity in both astronauts and animals. However, while space agencies have sought to deploy more women on their missions; animal models rarely include females studies or comparisons between males and females. Therefore, we exposed adult female rats to 2 weeks of partial weight-bearing at either 100% of their normal loading (PWB100) or 40% of their normal loading (PWB40), corresponding to Martian gravity-analog, and assess muscle function, force and histomorphometry. Females exposed to PWB showed an 11.62% decline in hindlimb grip force associated with an 11.84% decrease in soleus myofiber size after 14 days of exposure, while maintaining normal blood oxygenation and stress levels. This pilot study represents the first experiment designed to understand the muscular disuse associated with a partial reduction in mechanical loading in female rats, and the first step needed to develop successful mitigating strategies.

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

[This corrects the article DOI: 10.3389/fphys.2020.00302.].

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

As astronauts prepare to undertake new extra-terrestrial missions, innovative diagnostic tools are needed to better assess muscle deconditioning during periods of weightlessness and partial gravity. Electrical impedance myography (EIM) has been used to detect muscle deconditioning in rodents exposed to microgravity during spaceflight or using the standard ground-based model of hindlimb unloading via tail suspension (HU). Here, we used EIM to assess muscle changes in animals exposed to two new models: hindlimb suspension using a pelvic harness (HLS) and a partial weight-bearing (PWB) model that mimics partial gravity (including Lunar and Martian gravities). We also used a simple needle array electrode in lieu of surface or  EIM approaches previously employed. Our HLS results confirmed earlier findings obtained after spaceflight and tail suspension. Indeed, one EIM measure (i.e., phase-slope) that was previously reported as highly sensitive, was significantly decreased after HLS (day 0: 14.60 ± 0.97, day 7: 11.03 ± 0.81, and day 14: 10.13 ± 0.55 | Deg/MHz|,  < 0.0001), and was associated with a significant decrease in muscle grip force. Although EIM parameters such as 50 kHz phase, reactance, and resistance remained variable over 14 days in PWB animals, we identified major PWB-dependent effects at 7 days. Moreover, the data at both 7 and 14 days correlated to previously observed changes in rear paw grip force using the same PWB model. In conclusion, our data suggest that EIM has the potential to serve as biomarker of muscle deconditioning during exposure to both micro- and partial- gravity during future human space exploration.

Using Electrical Impedance Myography as a Biomarker of Muscle Deconditioning in Rats Exposed to Micro- and Partial-Gravity Analogs.

Ground-based animal models have been used extensively to understand the effects of microgravity on various physiological systems. Among them, hindlimb suspension (HLS), developed in 1979 in rats, remains the gold-standard and allows researchers to study the consequences of total unloading of the hind limbs while inducing a cephalic fluid shift. While this model has already brought valuable insights to space biology, few studies have directly compared functional decrements in the muscles of males and females during HLS. We exposed 28 adult Wistar rats (14 males and 14 females) to 14 days of HLS or normal loading (NL) to better assess how sex impacts disuse-induced muscle deconditioning. Females better maintained muscle function during HLS than males, as shown by a more moderate reduction in grip strength at 7 days (males: -37.5 ± 3.1%, females: -22.4 ± 6.5%, compared to baseline), that remains stable during the second week of unloading (males: -53.3 ± 5.7%, females: -22.4 ± 5.5%, compared to day 0) while the males exhibit a steady decrease over time (effect of sex × loading p = 0.0002, effect of sex × time × loading p = 0.0099). This was further supported by analyzing the force production in response to a tetanic stimulus. Further functional analyses using force production were also shown to correspond to sex differences in relative loss of muscle mass and CSA. Moreover, our functional data were supported by histomorphometric analyzes, and we highlighted differences in relative muscle loss and CSA. Specifically, female rats seem to experience a lesser muscle deconditioning during disuse than males thus emphasizing the need for more studies that will assess male and female animals concomitantly to develop tailored, effective countermeasures for all astronauts.

Marie Mortreux

Department of Neurology

Harvard Medical School - Beth Israel Deaconess Medical Center

Mimicking a Space Mission to Mars Using Hindlimb Unloading and Partial Weight Bearing in Rats

Performing In Vivo and Ex Vivo Electrical Impedance Myography in Rodents

Marie Mortreux

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Neurology

Harvard Medical School - Beth Israel Deaconess Medical Center

Mimicking a Space Mission to Mars Using Hindlimb Unloading and Partial Weight Bearing in Rats

Performing In Vivo and Ex Vivo Electrical Impedance Myography in Rodents

Department of Neurology