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Project Title:  Circadian Rhythm Disruption and Gravitational Disturbance in a Lunar Mission Analog: Consequences for Muscle Function During and After the Mission Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Vertebrate  
Start Date: 06/01/2023  
End Date: 05/31/2024  
Task Last Updated: 06/18/2023 
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Principal Investigator/Affiliation:   Mortreux, Marie  Ph.D. / University of Rhode Island 
Address:  Department of Nutrition 
45 Upper College Rd, 128 Fogarty Hall 
Kingston , RI 02881 
Phone: 617-667-3066  
Congressional District:
Organization Type: UNIVERSITY 
Organization Name: University of Rhode Island 
Joint Agency:  
Project Information: Grant/Contract No. 80NSSC23K1016 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Unique ID: 15533 
Solicitation / Funding Source: 2021 Space Biology NNH21ZDA001N-SBAS E.11: Animal Studies 
Grant/Contract No.: 80NSSC23K1016 
Project Type: GROUND 
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Space Biology Element: (1) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: (1) Musculoskeletal Biology
Space Biology Special Category: None
Task Description: Mechanical loading is the primary stimulus required for the maintenance and health of the musculoskeletal system. Exposure to microgravity or reduced gravity results in rapid bone loss and muscle atrophy, especially in the lower limbs. In recent years, the clock system in the skeletal muscle has been recognized to play a critical role in key aspects of muscle physiology, ranging from structural maintenance to functional regulation. On Earth, perturbations of the circadian rhythm affect muscle function and are associated with the development of sarcopenia. Reciprocally, studies have demonstrated that muscle activity can directly modulate the expression of muscle clock genes in a time-dependent fashion, and recent data suggest that the circadian clock could influence skeletal muscle adaptation in response to exercise training. Since Artemis astronauts will experience alterations in muscle condition and circadian rhythm simultaneously, it is critical to develop ground-based studies that will closely mimic this situation. While these stressors will occur temporarily, their effects may linger, and negatively influence muscle recovery after return from the mission. In this ground-based Early Career Investigator (ECI) proposal, I hypothesize that light cycle disturbances induced by a model of Chronic Jet Lag (CJL) will severely impact the peripheral muscle clock and, combined with altered gravity, will lead to additive negative effects during the disuse period. Moreover, I hypothesize that circadian disruption will have long-lasting effects that will significantly impair muscle recovery during the reloading period.

SA1: To characterize the impact of circadian disturbance and partial gravity in a lunar analog in male and female rats. 60 adult outbred rats (30/sex) will undergo 7 days of exposure to partial weight-bearing at 20% of normal loading (PWB20) to simulate lunar gravity. 1 group will be exposed to a regular light cycle (LD), 1 group will be kept in constant light to induce circadian free-running (LL), and the experimental group will be exposed to CJL using a 6h phase advance every other day.

SA2: To determine and compare the long-term effects of circadian disturbance and altered gravity during muscle recovery in males and females. 20 animals (10/sex) will be exposed to the same PWB20+CJL paradigm as in Aim 1. Animals will be allowed to recover for 7 days at normal loading (1g) and under a standard light cycle (LD).

For this work, I plan on first assessing muscle health and function through regular testing including grip strength, fatigue resistance, force production, and muscle quality. I will also monitor circadian parameters and rest/activity over several 24h periods. Finally, I will perform biomolecular assays in the suprachiasmatic nucleus and soleus muscle, targeting specific genes involved in circadian rhythm entrainment, muscle function, and inflammation.

This promising pilot study will help assess the additive effects of circadian disturbance in animals exposed to partial gravity and will help determine the existence of sex-based differences in response to spaceflight stressors. Moreover, I will determine sex-based differences during muscle recovery following disuse, and the long-term impact of circadian disturbance on muscle health and function. This study, which includes phenotypical and molecular outcomes, will assess the contribution of muscle clock genes and pathways to muscle health. Finally, targeted molecular assessment will help me use my diverse background (metabolism, neuromuscular, circadian) to explore other systems of interest that may be linked to muscle health and function (e.g., metabolic signaling pathways), and help characterize the key players that could be targeted with pharmacological approaches to provide new and effective countermeasures in future studies.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2023 
Task Progress: New project for FY2023.

Bibliography: Description: (Last Updated: ) 

Show Cumulative Bibliography
 None in FY 2023