The Rodent Research 3 (RR3) science investigation was sponsored by the Center for the Advancement of Science in Space (CASIS) in collaboration with Eli Lilly Company. The primary science objective of the mission was to evaluate muscle atrophy in microgravity conditions and to determine if inhibiting myostatin, a protein that negatively regulates muscle growth, could prevent the loss of muscle. Additional objectives were to assess whether preventing muscle wasting could mitigate the loss of bone mineral density under microgravity conditions and, through post-flight analysis, to quantify the effects of spaceflight on molecular markers of muscle atrophy and bone loss, with and without the myostatin inhibition.
Results from this investigation could lead to the reduction of negative impacts of spaceflight on the musculoskeletal systems of astronauts. Translational applications might include the development of treatments for muscle loss caused by ground-based diseases, disorders, and injuries, including muscular dystrophy, extended bed rest, advanced aging, casting, cancer cachexia, and kidney failure.
Two treatments were administered to the animals: One group received a control antibody and the other received an anti-myostatin antibody. Before launch, the mice were assessed for grip strength and scanned in a bone densitometer (DXA) under isoflurane gas anesthesia at launch minus 4 and launch minus 3 days. All twenty animals received treatment injections on the day of turnover (launch minus 1). The next injection session was held on orbit thirteen days later, after the mice were in microgravity for twelve days. After twenty-five days in microgravity, a functional measurement of grip strength was conducted on the animals, followed by treatment injections and DXA at twenty-six and twenty-eight days of microgravity. For these DXA scans, the animals were sedated with ketamine/xylazine and provided with thermal support from the Anesthesia Recovery System, to facilitate recovery. The experiment concluded with a second grip strength measurement at thirty-eight days in microgravity. Dissections were conducted over four days at thirty-nine to forty-two days in microgravity. Each dissection day consisted of five animals being dissected (the anti-myostatin and two control, or vice versa). Following euthanasia, blood was extracted via cardiac puncture, separated by centrifugation, and frozen. Right hind limbs were dissected and fixed in four percent paraformaldehyde, and carcasses were frozen. The frozen tissue samples were stored in the minus eighty degree freezer (MELFI). Hardware and tissue samples were returned to Earth for recovery and post-flight analyses. Biospecimens were delivered to CASIS.
Ground controls were conducted on a three-day delay at Kennedy Space Center in ISS environmental simulators (ISSESs) programmed with data from the Dragon capsule and the ISS cabin. Based on post-flight analysis of the RR-2 Habitat telemetry data, the ISSESs were programmed to be two degrees Celsius higher than the ISS cabin data; the result of this off-set was that the internal temperatures of the ground control habitats matched the flight Habitats closely for most of the experiment.
Results for this experiment are not targeted for archiving.
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