Time-dependency of morphological and molecular changes in the musculoskeletal system of mice exposed to the spaceflight environment (Rodent Research-2 (CASIS)) - 11.22.16

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Spaceflight causes major changes to the musculoskeletal system, including muscle atrophy and bone density loss, which mimic some of the symptoms of aging on Earth and pose a challenge for crew members living in space for extended periods. Time-dependency of morphological and molecular changes in the musculoskeletal system of mice exposed to the spaceflight environment (Rodent Research-2 [CASIS]) uses mice as model organisms of human health and studies how their bodies change at a molecular level. Results will help scientists discover new treatments for muscle- and bone-related diseases that affect people living in space and on Earth.
Science Results for Everyone
Information Pending

The following content was provided by Louis S. Stodieck, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Rodent Research-2

Principal Investigator(s)
Samuel Cadena, Novartis Institute for Biomedical Research, Cambridge, MA, United States

Co-Investigator(s)/Collaborator(s)
Information Pending

Developer(s)
NASA Ames Research Center, Moffett Field, CA, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Space Exploration, Earth Benefits, Scientific Discovery

ISS Expedition Duration
March 2015 - September 2015

Expeditions Assigned
43/44

Previous Missions

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Experiment Description

Research Overview

  • Spaceflight has significant and rapid effects on the musculoskeletal system; therefore, it is important to understand how bone and muscle are affected by spaceflight.
  • Rodent Research-2 (CASIS) has direct benefits to human health through understanding the effects of spaceflight on the musculoskeletal system of mice and applying that knowledge to understand the effects Earth-based human pathologies on muscle and bone.
  • The knowledge gained from this research will aid the greater scientific community in the development of novel therapies to treat muscle and bone in settings of prolonged spaceflight and chronic disease.

Description

Animal research is essential for understanding the impacts of space flight on physiological systems and for development of potential therapies that will mitigate detrimental responses to spaceflight. Researchers within the Novartis Institute for Biomedical Research in Cambridge, Massachusetts, are proposing to assess the morphological and molecular changes associated with muscle atrophy and bone loss caused by extended microgravity exposure from spaceflight. Specifically, the musculoskeletal effects of spaceflight as a function of duration of exposure to this unique environment will be characterized. The broader goal is to establish the utility of mice on board the International Space Station (ISS) to serve as models of serious musculoskeletal disease. Understanding and characterizing the effects of spaceflight on mice will potentially establish murine spaceflight models as an important new drug development tool by enabling the discovery of novel molecular targets for musculoskeletal diseases and pave the way for testing new therapeutics targeted to these diseases.
 
Previous studies have demonstrated the potential for murine models of musculoskeletal disease. However, data has been generated only for modest durations of exposure to low gravity of approximately 12-14 days and, with the Muscle Atrophy of Muscle Sparing in Transgenic Mice (Rodent Research-1 [CASIS]) mission, up to 21-34 days. A systematic characterization of the spaceflight environment has not been carried out due to practical and technical limitations with mission and hardware designs. The current study aims to characterize the time course of changes in the musculoskeletal tissues of mice exposed to varied lengths of spaceflight exposure (1, 2, 4 and 8 weeks). Time-dependency of morphological and molecular changes in the musculoskeletal system of mice exposed to the spaceflight environment (Rodent Research-2 [CASIS]) evaluates molecular changes (mRNA and protein) that occur in hind limb tissues of mice and correlate these with changes in structure, morphology, materials properties and function of muscle and bone.
 
In addition to the primary research focus on musculoskeletal systems, other organ systems are also studied for molecular and morphological changes as a function of duration of spaceflight exposure. These secondary objectives are expected to further characterize the potential use of mice in space to model human cardiovascular, immunological, ocular, metabolic and neurological diseases and disorders.

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Applications

Space Applications
Crew members living in microgravity experience severe and rapid loss of bone density and muscle mass, and so far exercise is the primary way to counteract it. The changes are most obvious in the parts of human bodies that bear weight, including the legs, hips and spine. This investigation studies muscle and bone loss in mice, especially in their hind legs, with a goal toward understanding molecular targets that can counteract these physical changes. Pharmaceutical drugs that may result from this experiment could benefit future crew members living in orbit or those on future trips to the moon, asteroids and Mars.

Earth Applications
People on Earth suffer from a variety of musculoskeletal disorders, from age-related atrophy to diseases like muscular dystrophy. The purpose of this investigation is to identify possible new drug targets and drug therapies for muscle and bone loss, directly benefiting patients on Earth. Eventual treatments derived from this research could benefit millions of people, from post-menopausal women to cancer patients and those with spinal cord injuries.

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Operations

Operational Requirements and Protocols

Twenty mice are flown for this experiment. The samples are returned via Dragon. Health and status data are downlinked daily.

Once the animals reach the ISS, the animal habitats are configured to receive the animals and are installed in EXPRESS rack. At specified times the animals are transferred from habitat to the Microgravity Sciences Glovebox (MSG) to perform experimental procedures such as injections or dissections. At the end of the experiment, animals are euthanized and hind legs dissected. From each mouse, one leg is frozen and the other fixed. Mice are also anesthetized and scanned in a bone densitometer at a midway point in the experiment. The frozen tissue samples are stored in MELFI and fixed tissue samples are stored in ambient stowage. After the final dissection day procedures are completed the habitats are bagged and stowed. The hardware and the tissue samples are returned to Earth for recovery.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites

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Imagery