|
Principal Investigator:
|
Susan A. Bloomfield, Ph.D.
|
|
Organization:
|
Texas A&M University
|
|
Project Ended:
|
2012
|
It is well documented that the human body loses bone and muscle mass during long-duration stays in space such as on the International Space Station. With the United States planning to conduct long-duration missions to the moon, scientists must learn what effects lunar gravity, which is one-sixth of Earth's, will have on human muscle and bone.
Dr. Susan A. Bloomfield is leading an animal model study to determine if muscle and bone loss on the moon will be as severe as it is in microgravity. Her project also seeks to determine if low-dose radiation exposure worsens bone and muscle loss in a lunar-gravity environment and if, under these unique conditions, exercise is still effective in reducing bone and muscle loss.
|
Principal Investigator:
|
Susan A. Bloomfield, Ph.D.
|
|
Organization:
|
Texas A&M University
|
|
Project Ended:
|
2012
|
The over-arching goal of this project is to determine if the usual bone and muscle loss observed during planetary missions will be exacerbated by exposure to space radiation. Using the partial g mouse model originally developed at MIT/Harvard by Drs Wagner and Bouxsein (the “partial g mouse”), we first performed experiments to verify whether the partial loading provided by a crew member’s body weight (1/6 g), or by body weight with spacesuit weight included (~1/3 g), would be enough to mitigate losses of bone and muscle. Additional analyses (micro-CT, histomorphometry, mechanical testing of bone) on tissues collected from our Experiment 1 in Year 1 were finalized this project year, enabling preparation of a manuscript to be submitted soon. These results confirm our original findings that 1/3 g is partially protective of cortical but not cancellous bone and that, for most bone outcomes, 1/6 and 1/3 BW loading do not prevent decrements in bone integrity observed with full hind limb unloading (simulating, e.g., low-earth orbit).
The major animal protocol work in Project Year 3 started with an intensive 5½-week stay at Brookhaven National Laboratory in June 2010 conducting a 3-week animal experiment testing responses to simulated galactic cosmic radiation in weight bearing (1 g) and partial (1/6) weight bearing mice, using 28Si, 300 MeV at the NASA Space Radiation Space Laboratory (NSRL). At experiment's end, we harvested multiple tissues beyond bone and muscle in hopes of tissue sharing with other PI’s, and have found at least one laboratory at NASA-JSC and another at Texas A&M interested in these extra tissues. The rest of this third project year focused on processing of these tissues as well as those from parallel x-ray experiments performed at Texas A&M late in Project Year 2.
Preliminary results derived from micro-CT analyses of distal femur cancellous bone from these two experiments indicate the highest doses of both x-ray and 28Si did exacerbate bone loss in our 1/6 g mice; these groups had 24% and 7% lower cancellous bone volume (%BV/TV) than sham exposed partial g mice. Interestingly, fractionating that highest dose protected against further loss of bone mass in the x-ray-exposed, but did not for silicon-exposed, mice on partial g. Micro-CT analyses of cancellous bone microarchitecture will soon be complemented by traditional histomorphometry measures of bone formation rate on both cancellous and cortical bone envelopes. Consistent suppression of femoral neck strength (load at failure) was observed in all partial g mice; this suppression was exacerbated in only one group exposed to low-dose radiation (17 cGy 28Si). Analyses in progress will provide some answers to potential mechanisms for these combined effects of reduced weight bearing and modeled space radiation (decreased bone formation? increased bone resorption? apoptosis of osteocytes/ osteoblasts?) which will address IRP Risk Degen 2 ("What are the mechanisms of degenerative tissue risks in the heart, circulatory, endocrine, digestive, lens and other tissue systems?").
We are also examining skeletal muscle alterations with partial weight bearing and modeled space radiation exposure; these analyses address IRP Risk M23 ("Do factors in addition to unloading contribute to muscle atrophy during space flight (e.g., radiation, inflammation, hydration, redox balance, energy balance)?") Analyses on 1/6 partial g mice reveal gastrocnemius muscle atrophy consistently occurring; some of this muscle loss is due to a reduced protein synthesis rate. However, there was no detectable additional effect of co-exposure to low dose x-rays on either loss of muscle mass or the reductions in protein synthesis rate. Western blot assessment of proteins that regulate peptide chain initiation vs. elongation will reveal mechanisms for any alterations in protein synthesis rates. Early results suggest that impairment in muscle protein metabolism with partial gravity may occur at the level of peptide-chain elongation. Upcoming assays will quantify BrdU-positive nuclei to indicate radiation-induced damage to satellite cells and, secondly, fiber-type specific changes in fiber cross-sectional area.
In the end, we will have a rich data base of both bone and muscle outcomes from parallel experiments performed with reference x-ray radiation and the 300MeV 28Si, with the capability of providing some calculations of relative biological effectiveness (RBE) for a number of physiological/structural outcomes. These experiments were designed to answer IRP Risk Degen 7 ["Are there significant synergistic effects from other spaceflight factors (microgravity, stress, altered circadian rhythms, changes in immune responses, etc.) that modify the degenerative risk from space radiation?"] in addition to IRP Risk B11 ("What are the effects of radiation on bone?")
In Year 4 (starting 6/1/2011) we will complete these analyses, prepare multiple manuscripts and conduct our final experiment to test whether acute high LET radiation exposure will impair the ability of bone and/or muscle to respond to a resistance-based training protocol administered during a 21-day period of partial weight bearing (at 1/6 g). To our knowledge, no other laboratories have tested this to date, so these data should be absolutely unique in the literature. NSRL beam time proposals were submitted to Brookhaven National Laboratory in February, 2010 and we await word of acceptance and scheduling, hopefully in the fall run, 2011. Mr. Brandon Macias, a senior doctoral student in Dr. Bloomfield’s laboratory and NSBRI Pre-Doctoral Fellow at Texas A&M, will be attending NASA’s Space Radiation Summer School in June 2011 at BNL, further enhancing our capabilities in radiation biology research.
|
Principal Investigator:
|
Susan A. Bloomfield, Ph.D.
|
|
Organization:
|
Texas A&M University
|
|
Project Ended:
|
2012
|
Defining the impact of partial weight bearing (as opposed to complete removal of weight bearing) has potentially important implications for rehabilitative strategies applied to stroke or spinal cord-injured patients. If the 1/6 body weight load bearing of our experimental animals, simulating the lunar environment, prove to mitigate the dramatic loss of mass and strength of both muscle and bone tissues seen with zero load bearing, mimicking the zero gravity conditions of spaceflight, then harness systems allowing for even minimal load bearing might help mitigate the profound changes seen in muscle strength and bone integrity in these patient populations.
Our experiments focusing on the effect of chronic exposure to low-dose radiation on musculoskeletal structure and function will provide unique and novel data about the potential degenerative effects experienced by those humans living in areas with high natural background radiation (e.g., Ramsar, Iran), Department of Energy/nuclear industry workers accumulating occupational exposures, and patients accumulating large exposures with multiple medical procedures.
Print