Rodent Research-8 (Rodent Research-8 (RR-8)) - 09.26.18

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

ISS Science for Everyone

Science Objectives for Everyone
Rodent Research-8 (RR-8) examines the physiology of aging and the effect of age on disease progression using groups of young and old mice flown in space and kept on Earth. Responses to spaceflight in humans and model organisms such as mice resemble certain aspects of accelerated aging. This investigation provides a better understanding of aging-related immune, bone, and muscle disease processes, which may lead to new therapies for use in space and on Earth.
Science Results for Everyone
Information Pending

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

OpNom: Rodent Research-8

Principal Investigator(s)
Michael S. Roberts, Ph.D., Center for the Advancement of Science in Space, Melbourne, FL, United States

Co-Investigator(s)/Collaborator(s)
Gretchen Kusek, Ph.D., Taconic Biosciences, Rensselaer, NY, United States

Developer(s)
Center for the Advancement of Science in Space (CASIS), Melbourne, FL, United States
Taconic Biosciences, Rensselae, NY, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Information Pending

ISS Expedition Duration
October 2018 - April 2019; -

Expeditions Assigned
57/58,59/60

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • Spaceflight has been shown to induce several physiological changes in humans and rodent models that resemble accelerated aging.
  • For the Rodent Research-8 (RR-8) investigation, young and old mice are flown to the International Space Station for 30 to 40-day or 60-day durations.
  • Tissue samples taken from the mice can provide researchers with better insight into disease processes related to bone loss, immune dysfunction, cardiovascular deconditioning, and loss of skeletal muscle mass and strength, to name a few. These insights may lead to new therapeutics for use in space or on Earth.

Description

The Rodent Research-8 (RR-8) investigation utilizes mice flown aboard the International Space Station (ISS), and maintained on Earth, to investigate the physiology of aging in response to microgravity and the role of aging in the onset and progression of disease. Two groups of 20 BALB/cAnNTac strain female mice (10 young and 10 old per group for a total of 40 mice) live aboard the ISS in specially designed rodent habitats for durations of one and two months.
 
The first group of young and old mice returns to Earth live after 30 to 40 days. The second group of animals remains on the ISS for approximately 60 days. In both cases, animals are euthanized humanely, and tissue samples are harvested for subsequent study and comparison with Earth-based control groups.
 
Tissues from space-flown rodents are rare and are extremely valuable, thus, there is great demand for access to these tissues from the research community - namely academic scientists, the pharmaceutical industry and government agencies, such as the Department of Defense (DoD) and the National Institutes of Health (NIH). The ability for researchers to gain access to these tissues is limited to relatively few opportunities to utilize the ISS, thus, there is urgency to maximize access via this investigation.
 
Specific Aim 1: To evaluate muscle atrophy under microgravity conditions, and to identify molecular pathways and targets that could be used to develop novel therapeutics for muscle disease. This aim focuses on hind limbs collected from groups of mice exposed to spaceflight for various lengths of time.
 
Specific Aim 2: To quantify changes in various molecular markers from several tissues, such as whole blood, brain, heart, lungs, kidney/adrenal glands, liver, spleen, and small intestines (some tissues are dissected in flight, and the remaining ones on Earth).
 
Specific Aim 3: To scan mice using a bone densitometer at mission middle, and end-points, to characterize the effects of microgravity on skeletal tissues. This is expected to establish the magnitude and time-course of bone loss during spaceflight exposure for future commercial bone drug testing.

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Applications

Space Applications
Changes induced by spaceflight in the human body and those of rodent models include bone loss, immune dysfunction, cardiovascular deconditioning, and loss of skeletal muscle mass and strength. Better understanding of these changes may lead to new countermeasures and therapies to protect astronaut health.

Earth Applications
On Earth, aging causes immune, bone, and muscle diseases. Better understanding of the processes of these diseases may lead to promising new therapies for patients on Earth.

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Operations

Operational Requirements and Protocols

Forty female BALB/cAnNTac mice are launched in 2 Transporters, transferred to 4 Rodent Habitats on board the ISS, and housed for up to 8 weeks. Twenty mice are in the 10-16 week old range (young), and the other 20 mice are in the 30-52 week old range (old) at launch. The Transporter 1 “young” mice (heretofore referred to as Group 1) are divided randomly into 2 groups of 10 each (10 mice in each Habitat with 5 mice on each side); while the Transporter 2 “old” mice (heretofore referred to as Group 2) are also similarly divided. Each group is exposed to the spaceflight environment for ~30 days (animals from both age groups), or 60 days (animals from both age groups).
 
Prior to SpaceX Dragon Vehicle unberth, half of the animals from each age group are transferred to the Dragon Vehicle and transported live back to Earth. After live animal return (~L+30 to +40 days), the remaining 20 mice from Groups 1 and 2 undergo mass measurements, and are then anesthetized via intraperitoneal (IP) injection of ketamine/xylazine, scanned by a bone densitometer, and recovered from anesthesia via IP injection of reversal drug and then placement into the Anesthesia Recovery System (ARS). Animals are then placed back into Habitats.
 
At 60 (± 2) days after exposure to microgravity, the remaining 20 mice undergo mass measurements, are anesthetized via IP injection of ketamine/xylazine/acepromazine, scanned with bone densitometer, then euthanized via ketamine/xylazine overdose injection and exsanguination. Spleens are taken from each mouse and fixed in RNAlater. The left hind limb is dissected from each mouse and preserved via formalin. The remaining hind limb remains attached and is frozen with the carcass.
 
Following the dissections, carcasses from all mice are frozen and stored at -80°C or lower, and returned to Earth for post-flight analysis. Video showing animal health and behavior is obtained and downlinked for archival recording and analysis.

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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