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Project Title:  Maintaining Musculoskeletal Health in the Lunar Environment Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2008  
End Date: 09/30/2012  
Task Last Updated: 04/04/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bloomfield, Susan A. Ph.D. / Texas A&M University 
Address:  Department of Health & Kinesiology 
400 Harvey Mitchell Pkwy, Suite 300 
College Station , TX 77843-4375 
Email: sbloom@tamu.edu 
Phone: 979-845-2871  
Congressional District: 17 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Texas A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Braby, Leslie  Texas Engineering Experiment Station 
Hogan, Harry  Texas A&M University 
Fluckey, James  Texas A&M University 
Wang, Suojin  Texas A&M University 
Project Information: Grant/Contract No. NCC 9-58-MA01602 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-MA01602 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) HHC1:Can partial gravity be simulated on Earth?
(2) HHC2:How does 1/6-g and 3/8-g influence countermeasures?
(3) Osteo04:We do not know the contribution of each risk factor on bone loss and recovery of bone strength, and which factors are the best targets for countermeasure application (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date change to 9/30/2012 (from 5/31/2012) per NSBRI (Ed., 1/24/2012)

Task Description: 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. A manuscript has been revised and submitted to the journal Medicine and Science in Sports and Exercise and is still in review. 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 hindlimb unloading (simulating, e.g., low-Earth orbit).

Continuing data analyses on experiments supporting Specific Aim 2 [Determine impact of low-dose, high LET radiation exposure (modeling that expected on the Lunar surface) on musculoskeletal outcomes in modeled Lunar gravity conditions] allowed for more refinement of conclusions reached during year 3. In support of our original hypothesis, radiation exposure exacerbates the loss of cancellous bone (%BV/TV) seen with partial weightbearing; it took only 0.5 Gy of 28Si exposure to produce the same 14% decline in %BV/TV as observed with 1 Gy of reference x-ray radiation. The primary effect on cancellous bone microarchitecture was a decrease in trabecular number but not trabecular thickness, suggesting more of an effect on osteoclast resorptive activity than on osteoblast formation activity, consistent with published literature. One of our most intriguing results was that fractionating the 0.5 Gy 28Si dose into 3 doses spread over the period of PWB produced the same net bone loss as did one acute dose delivered on the first day of PWB. By contrast, fractionating our 1 Gy x-ray exposure into 3 exposures DID effectively mitigate loss of bone.

The major task accomplished in Year 4 of this project was to complete experiments supporting our final specific aim: would low dose, high LET radiation impair the ability of bone and muscle to respond to exercise during recovery from a period of simulated Lunar gravity conditions? Marshaling all available budgetary means, we returned to NSRL at Brookhaven to test impact of simulated GCR on the exercise response in bone and muscle, rather than relying on reference (x-ray) radiation. During NSRL's Fall 2011 run, we successfully exposed ~65 mice to acute dose (0.5 Gy) of 56-Fe, before they were shipped to Texas A&M, where the animal protocols were conducted, finishing in April 2012. We have generated some exciting and novel data on vertebral bone responses to PWB and recovery there from: the 0.5 Gy 56Fe exposure appears to significantly impair the ability of spinal bone to regain cancellous bone mass lost during the preceding period of PWB. In fact, further losses in trabecular thickness are observed during the recovery period (with and without exercise), implying a sustained suppression of osteoblast activity from the radiation exposure imposed 6 weeks earlier. Similar findings held for cancellous bone in the distal femur, but the effects are less dramatic than in vertebral bone. Preliminary assessment of bone formation rate (BFR) on the periosteal surface of the tibial shaft indicates a significant reduction in this marker of osteoblast activity in this separate bone compartment. On-going histomorphometric analyses of BFR in the distal femur will help verify if high LET radiation also suppresses osteoblast function some 6 weeks later in cancellous bone.

We have also produced some novel data regarding skeletal muscle outcomes from combined partial weightbearing and simulated galactic cosmic radiation exposure. Simulated Lunar gravity resulted in significant decreases in muscle mass and rates of muscle protein synthesis. However, contrary to the working hypothesis, both ion species used (0.5 Gy28Si, 300 MeV or 0.5 Gy 56Fe, 1GeV), contributed to an increase in muscle wet mass. In viable muscle, alterations of muscle mass are associated with alterations of protein content that are proportional with water content. Thus, in healthy muscle, changes in muscle mass do not lead to changes in protein concentration within the tissue. Our analyses reveal that protein concentration was constant among groups in the 28Si groups, but not 56Fe groups. Furthermore, it appears that alterations in fractional synthesis rates (assessed using novel deuterium-oxide methodologies) were consistent with changes in protein concentrations, where lower FSRs were documented in tissues with lower protein concentrations. In summary, our results verify that the increases in gastrocnemius wet mass exposed to 0.5 Gy of 300 MeV 28Si are reflective of muscle gains, with or without the presence of partial loading. Gains due to 50cGy exposure of 1 GeV 56Fe appear to indicate an accumulation of extraneous, non-protein substances. 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?"] Understanding the interaction of reduced weightbearing and radiation exposure is an important goal in support of human exploration of space. Although not designed to thoroughly explain mechanisms for observed effects on bone and skeletal muscle, we are generating supporting analyses to provide some insight to direct future investigations.

Research Impact/Earth Benefits: Defining the impact of partial weightbearing (as opposed to complete non-weightbearing) has important implications for rehabilitative strategies applied to stroke or spinal cord-injured patients. Our results indicate that weightbearing at 1/6 or 1/3 of normal body weight does NOT mitigate the dramatic loss of mass and strength in both muscle and bone seen with zero load bearing (mimicking conditions of low-Earth orbit, e.g.). This implies that additional strategies beyond partial weightbearing that can be achieved with harness systems or walkers (such as active exercise of the affected limbs) is necessary to help minimize or reverse disuse-induced loss of muscle strength and bone integrity. Another population that stands to benefit from these data is composed of veterans returning home with traumatic brain injury, a major concern of the military these last 7 years.

Our experiments focusing on effects of low-dose radiation on musculoskeletal structure and function provide unique and novel data about the potential degenerative effects to be expected by those humans living in areas with high natural background radiation (e.g., Ramsar, Iran); by individuals who accumulate high occupational exposures to ionizing radiation (e.g., commercial airplane crews); and by patients accumulating multiple medical irradiation exposures over time. A growing literature is documenting surprising and deleterious effects on bone with low-level radiation (as opposed to the high doses used in radiotherapy for cancer patients) and our results are consistent with those findings, especially in bone sites rich in cancellous bone, such as the femoral neck (site of hip fractures) and in vertebral bone. Very little is known at the present time about the impact on these low doses on maintenance of normal muscle protein synthesis and muscle mass. Our early results suggest a surprising (but small) gain in muscle mass with very low dose, high LET radiation exposure, even during a period of partial weightbearing. However, protein synthesis appears to be impaired, so these gains in mass may not reflect gains in functional tissue (perhaps connective tissue).

Task Progress & Bibliography Information FY2012 
Task Progress: Specific Aim 1: We reworked a previously rejected manuscript extensively, adding new data, and submitted it in Dec 2012 to the journal Medicine and Science in Sports and Exercise.

Specific Aim 2 (impact of low-dose, high energy radiation simulating galactic cosmic radiation): All experiments were completed earlier; during Year 4 of this project we focused on finalizing histomorphometry analyses, muscle protein synthesis determinations and started on manuscript preparation. Experiment 2 (pilot experiment testing various doses of x-ray radiation in weightbearing mice, with primary cell culture studies) manuscript is in preparation for submission to the journal Radiation Research; progress has been slowed by the departure of the post-doctoral fellow (F. Lima) in charge, who has committed to a February, 2013 deadline. A second manuscript targeted to Radiation Research is being submitted in March 2013 detailing the impact of x-ray and high LET (28-Si) radiation exposures on cortical bone (B.R. Macias, first author); some of these data were also presented at the International Congress of Radiation Research (Warsaw, Poland; August, 2011) and at the American Society for Bone and Mineral Research, Annual Meeting (San Diego, CA; September, 2011). At least one other bone-oriented manuscript will be submitted as soon as we finalize the more labor-intensive histomorphometry analyses on cancellous bone from these experiments. Muscle protein synthesis and related cell signaling data (by Western blot) collection is now complete; histological assays for BrdUincorporation and fiber-type specific cross-sectional areas are in progress and should provide compelling data for several more manuscripts.

Specific Aim 3 (impact of simulated GCR on bone/muscle response to exercise during recovery from a period of partial weightbearing(PWB): We completed an extensive pilot experiment in summer of 2011 comparing the efficacy of two exercise paradigms in mitigating bone loss during a PWB period: treadmill running (endurance training) vs. tower climbing (more resistance based). (A manuscript of these data will be ready for submission to Acta Astronautica in late February, 2013; R. Boudreaux, first author.) Marshaling all available budgetary means, we returned to NSRL at Brookhaven to test impact of simulated GCR on the exercise response in bone and muscle, rather than relying on reference (x-ray) radiation. During NSRL's Fall 2011 run, we successfully exposed ~65 mice to acute dose (0.5 Gy) of 56-Fe, before they were shipped to Texas A&M, where the animal protocols were conducted, finishing in April 2012. All micro-CT analyses were finished by December 2012, as well as some mechanical testing results. On-going are histomorphometry analyses and skeletal muscle histology. We anticipate 2-3 more manuscripts will result from these data within the next 6 months.

Bibliography Type: Description: (Last Updated: 05/28/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Camp KA, Cunningham DA, Yuen E, Macias B, Solomon S, Hogan HA , Bloomfield SA. "Impact of omega-3 polyunsaturated fatty acids on bone during chronic simulated resistance training." 33rd Annual Meeting of the American Society for Bone and Mineral Research, San Diego, California, September 16-20, 2011.

J Bone Miner Res. 2011;26(Suppl 1). , Sep-2011

Abstracts for Journals and Proceedings Cunningham DA, Camp KA, Yuen E, Macias B, Solomon S, Hogan HA, Bloomfield SA. "Ibuprofen administered pre- or post-simulated resistance exercise training does not diminish gains in bone formation or bone mass." 33rd Annual Meeting of the American Society for Bone and Mineral Research, San Diego, California, September 16-20, 2011.

J Bone Miner Res. 2011;26(Suppl 1). , Sep-2011

Abstracts for Journals and Proceedings Yuen E, Morgan J, Zwart SR, Gonzales E, Camp K, Macias BR, Smith SM, Bloomfield SA. "High dietary iron and 137Cs radiation exposure induce oxidative stress and reduce bone mass." Experimental Biology 2012, San Diego, CA, April 21-25, 2012.

FASEB Journal. 2012 Apr;26(Meeting Abstract Supplement):641.28. , Apr-2012

Abstracts for Journals and Proceedings Macias BR, Yuen E, Camp K, Boudreaux R, Metzger C, Morgan S, Shirazi-Fard Y, Hogan HA, Bloomfield S. "Inhibition of Glycogen Synthase Kinase-3ß Combined with Simulated Resistance Exercise during Hindlimb Unloading Prevents Femoral Neck and Mid-Shaft Tibia Cortical Bone Loss." 4th Joint Meeting of the European Calcified Tissue Society and International Bone and Mineral Society; Stockholm, Sweden, May 19-23, 2012.

Bone. 2012 May;50(Suppl 1):S124. http://dx.doi.org/10.1016/j.bone.2012.02.385 , May-2012

Abstracts for Journals and Proceedings Macias RM, Lima F, Shirazi-Fard Y, Cunningham DA, Yuen E, Camp K, Wiggs MP, Fluckey JD, Greene ES, Allen MR, Braby LA, Hogan HA, Bloomfield SA. "Partial weightbearing for 21-days and low dose high energy radiation results in cancellous and cortical bone loss." 33rd Annual Meeting of the American Society for Bone and Mineral Research, San Diego, California, September 16-20, 2011.

J Bone Miner Res. 2011;26(Suppl 1). , Sep-2011

Abstracts for Journals and Proceedings Shimkus KL, Wiggs M, Macias BR, Lima F, Boudreaux RD, Shirazi-Fard Y, Greene E, Braby L, Hogan HA, Bloomfield SA, Fluckey J. "Space Radiation Environment Increases Muscle Mass in Simulated Lunar Gravity." 2012 APS Intersociety Meeting: Integrative Biology of Exercise, Westminster, CO, October 10-13, 2012.

2012 APS Intersociety Meeting: Integrative Biology of Exercise, Westminster, CO, October 10-13, 2012. Program and Abstracts, Abstract 23.1, p. 41. , Oct-2012

Abstracts for Journals and Proceedings Boudreaux R, Metzger C, Cecchini T, Camp K, Yuen E, Macias B, Shirazi-Fard Y, Hogan H, Bloomfield S. "Treadmill Running and Tower Climbing Resistance Exercise Mitigate Disuse Bone Loss in Mice Equally Well." Texas Chapter of the American College of Sports Medicine 2012 meeting, Austin, TX, March 1–2, 2012.

International Journal of Exercise Science: Conference Abstract Submissions: 2012;2(4):Article 3. Available at: http://digitalcommons.wku.edu/ijesab/vol2/iss4/3 , Mar-2012

Articles in Peer-reviewed Journals Macias BR, Swift JM, Nilsson MI, Hogan HA, Bouse SD, Bloomfield SA. "Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse." J Appl Physiol. 2012 Mar;112(5):918-25. Epub 2011 Dec 15. http://dx.doi.org/10.1152/japplphysiol.00978.2011 ; PubMed PMID: 22174402 , Mar-2012
Articles in Peer-reviewed Journals Swift JM, Hogan HA, Bloomfield SA. "ß-1 Adrenergic agonist mitigates unloading-induced bone loss by maintaining formation." Med Sci Sports Exerc. 2013 Sep;45(9):1665-73. https://doi.org/10.1249/MSS.0b013e31828d39bc ; PubMed PMID: 23470310 , Sep-2013
Articles in Peer-reviewed Journals Boudreaux RD, Metzger CE, Macias BR, Shirazi-Fard Y, Hogan HA, Bloomfield SA. "Bone loss during partial weight bearing (1/6th gravity) is mitigated by resistance and aerobic exercise in mice." Acta Astronaut. 2014 Jun-Jul;99:71-7. http://dx.doi.org/10.1016/j.actaastro.2014.02.015 , Jun-2014
Articles in Peer-reviewed Journals Boudreaux RD, Swift JM, Gasier HG, Wiggs MP, Hogan HA, Fluckey JD, Bloomfield SA. "Increased resistance during jump exercise does not enhance cortical bone formation." Med Sci Sports Exerc. 2014;46(5):982-9. http://dx.doi.org/10.1249/MSS.0000000000000195 ; PubMed PMID: 24743108; PubMed Central PMCID: PMC3992436 , Jan-2014
Articles in Peer-reviewed Journals Swift SN, Swift JM, Bloomfield SA. "Mechanical loading increases detection of estrogen receptor-alpha in osteocytes and osteoblasts despite chronic energy restriction." J Appl Physiol (1985). 2014 Dec 1;117(11):1349-55. Epub 2014 Sep 11. http://dx.doi.org/10.1152/japplphysiol.00588.2013 ; PubMed PMID: 25213639 , Dec-2014
Articles in Peer-reviewed Journals Macias BR, Lima F, Swift JM, Shirazi-Fard Y, Greene ES, Allen MR, Fluckey J, Hogan HA, Braby L, Wang S, Bloomfield SA. "Simulating the lunar environment: Partial weightbearing and high-LET radiation-induce bone loss and increase sclerostin-positive osteocytes." Radiat Res. 2016 Sep;186(3):254-63. http://dx.doi.org/10.1667/RR13579.1 ; PubMed PMID: 27538114 , Sep-2016
Articles in Peer-reviewed Journals Lee TV, Lee CW, Chen VCW, Bui S, Fluckey JD, Riechman SE. "The effects of hindlimb unloading versus dietary cholesterol and resistance training on rat skeletal muscle responses." Lipids Health Dis. 2019 Jan 5;18(1):3. https://doi.org/10.1186/s12944-018-0944-9 ; PubMed PMID: 30611265; PubMed Central PMCID: PMC6320614 , Jan-2019
Articles in Peer-reviewed Journals Lima F, Swift JM, Greene ES, Allen MR, Cunningham DA, Braby LA, Bloomfield SA. "Exposure to low-dose X-ray radiation alters bone progenitor cells and bone microarchitecture." Radiat Res. 2017 Oct;188(4):433-42. Epub 2017 Aug 3. https://doi.org/10.1667/RR14414.1 ; PubMed PMID: 28771086 , Oct-2017
Awards Macias B. "NSBRI Post-Doctoral Fellowship, October 2012." Oct-2012
Awards Macias B. "Texas A&M Dept of Health & Kinesiology Distinguished Honor Graduate Student, December 2012." Dec-2012
Awards Elmer K. "Texas A&M College of Education Undergraduate Research Award, September 2012." Sep-2012
Awards Boudreaux R. "NSBRI Pre-Doctoral Space Life Science Fellowship, January 2012." Jan-2012
Awards Boudreaux R. "Texas Space Grant Fellowship, June 2012." Jun-2012
Awards Wang S. "Editor-in-Chief, Journal of Nonparametric Statistics, December 2011." Dec-2011
Books/Book Chapters Bloomfield SA, Metzger CE. "Novel findings in bone biology: impact on bone health for women." in "Integrative Physiology of Women's Health." Ed. E. Spangenberg. New York : Springer, 2013. p. 17-33. https://doi.org/10.1007/978-1-4614-8630-5_2 , Sep-2013
Project Title:  Maintaining Musculoskeletal Health in the Lunar Environment Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2008  
End Date: 09/30/2012  
Task Last Updated: 06/08/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bloomfield, Susan A. Ph.D. / Texas A&M University 
Address:  Department of Health & Kinesiology 
400 Harvey Mitchell Pkwy, Suite 300 
College Station , TX 77843-4375 
Email: sbloom@tamu.edu 
Phone: 979-845-2871  
Congressional District: 17 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Texas A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Braby, Leslie  Texas Engineering Experiment Station 
Hogan, Harry  Texas A&M University 
Fluckey, James  Texas A&M University 
Wang, Suojin  Texas A&M University 
Project Information: Grant/Contract No. NCC 9-58-MA01602 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-MA01602 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates: 13 
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) HHC1:Can partial gravity be simulated on Earth?
(2) HHC2:How does 1/6-g and 3/8-g influence countermeasures?
(3) Osteo04:We do not know the contribution of each risk factor on bone loss and recovery of bone strength, and which factors are the best targets for countermeasure application (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date change to 9/30/2012 (from 5/31/2012) per NSBRI (Ed., 1/24/2012)

Task Description: 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 hindlimb unloading (simulating, e.g., low-earth orbit).

The major animal protocol work in Project Year 3 started with an intensive 5 ½ week stay at Brookhaven National Laboratory in June 2010 conducting a 3-week animal experiment testing responses to simulated galactic cosmic radiation in weightbearing (1 g) and partial (1/6) weightbearing 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 weightbearing 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 weightbearing 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 weightbearing (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.

Research Impact/Earth Benefits: Defining the impact of partial weightbearing (as opposed to complete non-weightbearing) has important implications for rehabilitative strategies applied to stroke or spinal cord-injured patients. Should the 1/6 or 1/3 g conditions in our experimental animals prove to mitigate the dramatic loss of mass and strength in both muscle and bone seen with zero load bearing (mimicking conditions of low-earth orbit, e.g.), then harness systems or walkers allowing for even minimal load bearing offer high potential for mitigating changes seen in muscle strength and bone integrity in these patients populations. Another population that stands to benefit from these data is composed of veterans returning home with traumatic brain injury, a major concern of the military these last 7 years.

Our experiments focusing on effects of low-dose radiation on musculoskeletal structure and function will provide unique and novel data about the potential degenerative effects to be expected by those humans living in areas with high natural background radiation (e.g., Ramsar, Iran); by individuals who accumulate high occupational exposures to ionizing radiation (e.g., commercial airplane crews); and by patients accumulating multiple medical irradiation exposures over time. A growing literature is documenting surprising and deleterious effects on bone with low-level radiation (as opposed to the high doses used in radiotherapy for cancer patients); very little is known at the present time about the impact on these low doses on maintenance of normal muscle protein synthesis and muscle mass. Our experiments directly address these issues.

Task Progress & Bibliography Information FY2011 
Task Progress: Specific Aim 1 [does modeled Lunar gravity, with or without additional weight of EVA spacesuit, protect against decrements in musculoskeletal structure and/or function]:

A manuscript comparing is nearly ready for submission by 5/31/2011; target journal is Bone. Poster presentations including these data were made at the Oct 2010 meetings of the American Society of Bone & Mineral Research. A separate manuscript detailing muscle outcomes (muscle protein synthesis, satellite cell BrdU incorporation, histological assessment of fiber cross-sectional areas) is in preparation.

Specific Aim 2 [ impact of low-dose radiation simulating galactic cosmic radiation on the musculoskeletal response to partial weightbearing]:

Our Experiment 2 (performed 6/09-3/10) was a comprehensive pilot experiment testing the impact of low doses of reference x-ray radiation. These results have been reported in poster presentations at the Oct 2010 meetings of the American Society of Bone & Mineral Research (ASBMR) (Lima et al., JBMR 2010) and a manuscript is in preparation for submission to Radiation Research by July 1, 2011. Experiment 3, testing the combined effect of reference x-ray radiation (50 and 100 cGy) and partial weightbearing (1/6 g), was completed in Year 2; much of the current project year has been devoted to analysis of tissues collected (histomorphometry analyses, mechanical testing, immunostaining). Muscle protein synthesis assays are nearly complete; histological assays for BrdU incorporation and fiber-type specific cross-sectional areas are in progress.

Experiment 4 was performed entirely on site at Brookhaven's NSRL in June 2010 at start of Year 3 to test the combined impact of high LET radiation (17 and 50 cGy of 28Si, 300 MeV) and partial weightbearing (1/6 g), parallelling as closely as possible Experiment 3 described above. The balance of our year has been spent in processing tissue analyses from bone and muscle collected during this experiment and in planning for our final Year 4 experiments; beam time and animal use proposals submitted to BNL 2/11 for fall 2011 run). Preliminary results from Experiments 3 and 4 have been presented at the April 2011 IAA Humans in Space Symposium (Houston, TX) and May 2011 joint meetings of the European Calcified Tissue Society and the International Bone and Mineral Society in Athens, Greece. Additional abstracts were submitted for presentation at the September 2011 meetings of the American Society of Bone & Mineral Research (San Diego, CA). Muscle protein synthesis assays are nearly complete; histological assays for BrdU incorporation and fiber-type specific cross-sectional areas are in progress.

Bibliography Type: Description: (Last Updated: 05/28/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lima F, Swift JM, Greene ES, Allen MR, Cunningham DA, Braby L, Bloomfield SA. "Effect of low dose ionizing radiation on bone microarchitecture and bone marrow progenitor differentiation." Presented at the 2010 American Society of Bone and Mineral Research Annual Meeting; Toronto, Ontario, Canada, October 15-19, 2010.

J Bone Miner Res 2010 Sep; 25(Suppl 1):SU0091. Available at: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=1f73ef75-f01a-4539-94ae-344ffa8b3616 ; accessed 6/09/2011. , Sep-2010

Abstracts for Journals and Proceedings Lima F, Swift JM, Macias BR, Greene ES, Kupke JS, Shirazi-Fard Y, Allen MR, Hogan HA, Bloomfield SA. "Weight bearing in simulated 1/6th and 1/3rd gravity does not prevent bone loss." Presented at the 2010 American Society of Bone and Mineral Research Annual Meeting; Toronto, Ontario, Canada, October 15-19, 2010.

J Bone Miner Res 2010 Sep;25(Suppl 1):MO0094. Available at: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=98e55093-2296-42ea-9899-5654faad070c ; accessed 6/09/2011. , Sep-2010

Abstracts for Journals and Proceedings Swift JM, Swift S, Allen M, Lima F, Bloomfield SA. "Beta-1 adrenergic administration mitigates negative changes in cancellous bone microarchitecture and inhibits osteocyte apoptosis during disuse." Presented at the 2010 American Society of Bone and Mineral Research Annual Meeting; Toronto, Ontario, Canada, October 15-19, 2010.

J Bone Miner Res 2010 Sep;25(Suppl 1):SA0319. Available at: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=a8043d81-b402-419b-a6ed-81ba8c2104b9 ; accessed 6/09/2011. , Sep-2010

Abstracts for Journals and Proceedings Swift JM, Swift SN, Bouse SD, Hogan HA, Bloomfield SA. "Alendronate inhibits bone formation response to simulated resistance training during disuse." American College of Sports Medicine 57th Annual Meeting, Baltimore, MD, June 2-5, 2010.

Medicine & Science in Sports & Exercise 2010 May;42(5 Suppl):704. http://dx.doi.org/10.1249/01.MSS.0000386048.59831.72 , May-2010

Articles in Peer-reviewed Journals Swift JM, Gasier HG, Swift SN, Wiggs MP, Hogan HA, Fluckey JD, Bloomfield SA. "Increased training loads do not magnify cancellous bone gains with rodent jump resistance exercise." J Appl Physiol. 2010 Dec;109(6):1600-7. PubMed PMID: 20930128 , Dec-2010
Articles in Peer-reviewed Journals Swift JM, Swift SN, Nilsson MI, Hogan HA, Bouse SD, Bloomfield SA. "Cancellous bone formation response to simulated resistance training during disuse is blunted by concurrent alendronate treatment." J Bone Miner Res. 2011 Sep;26(9):2140-50. Epub 2011 Apr 20. http://dx.doi.org/10.1002/jbmr.407 ; PMID: 21509821 , Sep-2011
Articles in Peer-reviewed Journals Carpenter RD, Lang TF, Bloomfield SA, Bloomberg JJ, Judex S, Keyak JH, Midura RJ, Pajevic PD, Spatz JM. "Effects of long-duration spaceflight, microgravity, and radiation on the neuromuscular, sensorimotor, and skeletal systems." The Human Mission to Mars: Colonizing the Red Planet. Journal of Cosmology 2010 Oct- Nov;12:3778-80. http://journalofcosmology.com/Mars147.html , Oct-2010
Awards Macias B. "NSF Graduate Fellowship, September 2010." Sep-2010
Awards Bloomfield SA. "Armstrong Research Scholar Award (Health & Kinesiology, TAMU), May 2011." May-2011
Awards Shirazi Y. "Graduate Student Poster Award (5th), IAA Humans in Space Symposium, April 2011." Apr-2011
Dissertations and Theses Kupke JS. "Characterization of the Femoral Neck Region's Response to the Rat Hindlimb Unloading Model through Tomographic Scanning, Mechanical Testing and Estimated Strengths." MS Thesis, Texas A&M University, December, 2010. , Dec-2010
Project Title:  Maintaining Musculoskeletal Health in the Lunar Environment Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 08/06/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bloomfield, Susan A. Ph.D. / Texas A&M University 
Address:  Department of Health & Kinesiology 
400 Harvey Mitchell Pkwy, Suite 300 
College Station , TX 77843-4375 
Email: sbloom@tamu.edu 
Phone: 979-845-2871  
Congressional District: 17 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Texas A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Braby, Leslie  Texas Engineering Experiment Station 
Hogan, Harry  Texas A&M University 
Fluckey, James  Texas A&M University 
Project Information: Grant/Contract No. NCC 9-58-MA01602 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-MA01602 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) HHC1:Can partial gravity be simulated on Earth?
(2) HHC2:How does 1/6-g and 3/8-g influence countermeasures?
(3) Osteo04:We do not know the contribution of each risk factor on bone loss and recovery of bone strength, and which factors are the best targets for countermeasure application (IRP Rev E)
Task Description: The over-arching purpose of this project is to determine if the usual bone and muscle loss observed during spaceflight will be mitigated by the moon's partial (1/6 g) gravity, if radiation exposure exacerbates bone/muscle loss at this reduced loading level, and if exercise is effective in mitigating such losses under these conditions. This requires an effective model of the Lunar environment, simulating conditions during Lunar outpost missions. We will use a novel partial gravity mouse model to first determine the independent impact of 1/6 g on multiple bone and muscle outcomes, including direct determinations of bone breaking strength and other mechanical properties. We will then test the additional impact of low dose radiation modeling galactic cosmic radiation (GCR) during partial gravity conditions by exposing these mice to one acute dose, or 4 fractionated doses on a weekly basis, of ionizing radiation. Data from these experiments will be used to justify expanded experiments at the Brookhaven NASA Space Radiation Laboratory utilizing heavy iron ions to simulate galactic cosmic radiation. Finally, the impact of the Lunar environment (partial gravity plus modeled space radiation) on the musculoskeletal response to exercise countermeasures.

Experiments supporting Specific Aim 1 [does partial weightbearing (~1/6 g) mitigate losses observed with full unloading (~ 0 g)] are just concluding in early June 2009, hence we are not yet able to report on key findings. We have made a "course correction" in the design of those first experiments. To simulate the additional loadbearing incurred by crew members locomoting on the Lunar surface due to the weight of EVA spacesuits, we elected to add one additional group of animals designated "1/3 g" (since current spacesuit design is roughly equivalent to one body weight, hence doubling the load bearing in the 1/6 g environment). This is easily accommodated by our partial g mouse model, since weightbearing can be titrated to whatever fraction of 100% body weight is desired.

We are concurrently preparing to start Experiment 2 (supporting Specific Aim 2: does low-dose radiation exposure change the bone or muscle response to partial gravity). This is a dose-response study utilizing reference x-ray radiation to assess responses of bone and muscle at early (~3 days), "delayed" (~21 days) and "recovery" (~56 days) time points. To achieve the best sensitivity possible, we have added cell culture studies to this experiment at the earlier timepoints to assess the impact on osteoprogenitor cell populations in the marrow. Pilot experiments are in progress to verify our procedures with primary cell culture.

Year 2 of this project will hence start with Experiment 2 (beginning July 2009) utilizing 108 mice (12 groups of 9 each) to test responses at the 3 time points listed above at 3 different radiation exposures. We will choose the lowest radiation dose producing detectable change in muscle protein synthesis and bone formation rate to use in the subsequent Experiment 3, commencing in February 2010, which will test the effects of x-ray exposure on the response to simulated partial gravity; in this experiment, mice subjected to 1/3 g (and weightbearing control mice) will be exposed to one acute dose of x-ray (low LET) radiation as well as 3 fractionated doses. Results of Experiment 2 will also be critical to constructing a beam time proposal for a repetition of Experiment 3 at Brookhaven National Lab during Year 3 of this project.

The project PI (S. Bloomfield) is attending NASA's Space Radiation Summer School at Brookhaven National Laboratory in June 2009. Both the conceptual and practical knowledge gained will prove invaluable for the later preparation of a beam time proposal as well as preparing for the logistics of conducting 3-week long experiments with live animals at the NASA Space Radiation Laboratory facility.

Research Impact/Earth Benefits: Defining the impact of partial weightbearing (as opposed to complete non-weightbearing) has important implications for rehabilitative strategies applied to stroke or spinal cord-injured patients. Should the 1/6 or 1/3 g conditions in our experimental animals prove to mitigate the dramatic loss of mass and strength in both muscle and bone seen with zero load bearing (mimicking conditions of low-earth orbit, e.g.), then harness systems or walkers allowing for even minimal load bearing offer high potential for mitigating changes seen in muscle strength and bone integrity in these patients populations. Another population that stands to benefit from these data is the growing number of returning veterans with traumatic brain injury.

Our experiments focusing on effects of low-dose radiation on musculoskeletal structure and function will provide unique and novel data about the potential degenerative effects to be expected by those humans living in areas with high natural background radiation (e.g., Ramsar, Iran), by individuals that accumulate high occupational exposures to ionizing radiation (e.g., commercial airplane crews), and by patients accumulating multiple medical irradiation exposures over time. A growing literature is documenting surprising and deleterious effects on bone with low-level radiation (as opposed to the high doses used in radiotherapy for cancer patients); very little is known at the present time about the impact on muscle.

Task Progress & Bibliography Information FY2010 
Task Progress: Specific Aim 1 [does modeled Lunar gravity protect, with or without additional weight of EVA spacesuit, protect against decrements in musculoskeletal structure and/or function]: The live animal experiments were completed in the first week of Year 2. Virtually all analyses from this Experiment 1 have been completed: pQCT data collected at days 0 and 21; micro CT scans of excised distal femurs; histomorphometric measures of cancellous bone microarchitecture and bone formation rate at cortical/cancellous bone sites; mechanical testing of tibiae and radii; fecal corticosterone levels to assess animal stress; TUNEL staining for osteocyte apoptosis; and muscle outcomes (wet weights, fractional protein synthesis rate, BrdU incorporation to assess satellite cells, gene expression of markers for protein anabolism). These outcomes were reported at 2010 Experimental Biology meetings (April, Anaheim, CA); first manuscripts are in progress.

Specific Aim 2 [impact of low-dose radiation simulating galactic cosmic radiation on the musculoskeletal response to partial weightbearing]: We first completed a dose-response experiment to determine the best dose of x-ray radiation to use in Experiment 3, as well as timing of animal sacrifice after the radiation exposure. In the summer of 2009, mice were exposed to 0 (sham), 17, or 50 or 100 cGy of reference x-ray radiation; one group was sacrificed 3 days after exposure and a second group at 21 days. Micro-CT analyses of distal femurs, histological assessment of bone formation rate, were completed. A significant addition to this experiment was performance of primary cell culture studies of bone marrow stromal cells (BMSC) to assess radiation effects on BMSC proliferative and differentiation capabilities. An additional round of mice were irradiated in spring of 2010 to repeat cell culture experiments. Most analyses have been completed; preliminary results will be presented at the 2010 Skeletal Tissue Biology Workshop (Sun Valley, August, 2010) and at the American Society for Bone & Mineral Research (Toronto, October 2010).

The main experiment for Specific Aim 2 (Experiment 3) was completed by April 2010; both weightbearing (1 g) and partial (1/6) g mice were exposed to sham irradiation or 1 dose of 17 or 50 cGy of x-ray radiation on Day 0. A fourth group was exposed to 3 fractionated doses (0.17 Gy at 1 week intervals, on Day 0, 7 and 14). Animals were sacrificed after 21 days; analysis of bone and muscle collected at sacrifice are on-going. April and May of 2010 has been dominated by planning for experiments at the NASA Space Radiation Laboratory at Brookhaven National Laboratory, which will expose weightbearing and partial (1/6) g mice to similar doses of a higher LET ionizing radiation (silicon). These experiments are scheduled for the Summer 2010 run, starting on May 31.

Bibliography Type: Description: (Last Updated: 05/28/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lima F, Nilsson MI, Bouse S, Hogan HA, Swift SN, Bloomfield SA. "Alendronate inhibits disuse bone loss in dose-dependent manner in mature male rats." 31st Annual Meeting of the American Society for Bone and Mineral Research, Denver, CO, September 11-15, 2009.

J Bone Miner Res. 2009 Sep;24(Suppl 1). Available at http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=0ad3c165-74d5-452f-96e2-661da47b6166 , Sep-2009

Abstracts for Journals and Proceedings Macias BR, Swift JM, Lima F, Greene ES, Allen MR, Bloomfield SA. "Weightbearing in simulated 1/6th and 1/3rd gravity does not prevent cancellous bone loss." Experimental Biology 2010, Anaheim, CA, April 24-28, 2010.

FASEB J. 2010 Apr;4. , Apr-2010

Abstracts for Journals and Proceedings Swift JM, Gasier HG, Wiggs MP, Swift SN, Bouse SD, Hogan HA, Fluckey JD, Bloomfield SA. "Increased strain magnitude during rodent voluntary dynamic exercise does not further enhance the anabolic skeletal response." 31st Annual Meeting of the American Society for Bone and Mineral Research, Denver, CO., September 11-15, 2009.

J Bone Miner Res. 2009 Sep;24(Suppl 1). Available at http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=af138fdb-3efd-49ab-a870-3e07ad059658 , Sep-2009

Abstracts for Journals and Proceedings Wiggs MP, Fluckey JD, Swift JM, Lima F, Greene ES, Bloomfield SA. "The effect of simulated 1/6th and 1/3rd gravity on gastrocnemius muscle mass and fractional protein synthesis in mice." Experimental Biology 2010, Anaheim, CA., April 24-28, 2010.

FASEB J 2010 Apr;24. , Apr-2010

Articles in Peer-reviewed Journals Bloomfield SA. "Disuse osteopenia." Curr Osteoporos Rep. 2010 Jun;8(2):91-7. PMID: 20425616 , Jun-2010
Articles in Peer-reviewed Journals Swift JM, Gasier HG, Swift SN, Wiggs MP, Hogan HA, Fluckey JD, Bloomfield SA "Increased training loads do not magnify cancellous bone gains with rodent jump resistance exercise." Bone. In press, 2010. , Aug-2010
Articles in Peer-reviewed Journals Swift JM, Nilsson MI, Hogan HA, Sumner LR, Bloomfield SA. "Simulated resistance training during hindlimb unloading abolishes disuse bone loss and maintains muscle strength." J Bone Miner Res. 2010 Mar;25(3):564-74. PMID: 19653816 , Mar-2010
Awards Swift JM. "Texas A&M Assoc. of Former Students Distinguished Graduate Student Excellence in Research Award, April 2010." Apr-2010
Awards Wang S. "Editor-in-Chief, Journal of Nonparametric Statistics, November 2009." Nov-2009
Awards Wang S. "Texas A&M System Teaching Excellence Award, October 2009." Oct-2009
Dissertations and Theses Bouse S. "Investigation of transfer function analysis as a means to predict strain on rat tibiae from ankle torque waveforms." Thesis, Texas A&M University, December 2009. , Dec-2009
Dissertations and Theses Lucas MW. "A novel method for the evaluation of mechanical properties of cancellous bone in the rat distal femur." Dissertation or Thesis, August 2009. , Aug-2009
Project Title:  Maintaining Musculoskeletal Health in the Lunar Environment Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 07/10/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bloomfield, Susan A. Ph.D. / Texas A&M University 
Address:  Department of Health & Kinesiology 
400 Harvey Mitchell Pkwy, Suite 300 
College Station , TX 77843-4375 
Email: sbloom@tamu.edu 
Phone: 979-845-2871  
Congressional District: 17 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Texas A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Braby, Leslie  Texas Engineering Experiment Station 
Hogan, Harry  Texas A&M University 
Fluckey, James  Texas A&M University 
Project Information: Grant/Contract No. NCC 9-58-MA01602 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-MA01602 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) HHC1:Can partial gravity be simulated on Earth?
(2) HHC2:How does 1/6-g and 3/8-g influence countermeasures?
(3) Osteo04:We do not know the contribution of each risk factor on bone loss and recovery of bone strength, and which factors are the best targets for countermeasure application (IRP Rev E)
Task Description: The over-arching purpose of this project is to determine if the usual bone and muscle loss observed during spaceflight will be mitigated by the moon's partial (1/6 g) gravity, if radiation exposure exacerbates bone/muscle loss at this reduced loading level, and if exercise is effective in mitigating such losses under these conditions. This requires an effective model of the Lunar environment, simulating conditions during Lunar outpost missions. We will use a novel partial gravity mouse model to first determine the independent impact of 1/6 g on multiple bone and muscle outcomes, including direct determinations of bone breaking strength and other mechanical properties. We will then test the additional impact of low dose radiation modeling galactic cosmic radiation (GCR) during partial gravity conditions by exposing these mice to one acute dose, or 4 fractionated doses on a weekly basis, of ionizing radiation. Data from these experiments will be used to justify expanded experiments at the Brookhaven NASA Space Radiation Laboratory utilizing heavy iron ions to simulate galactic cosmic radiation. Finally, the impact of the Lunar environment (partial gravity plus modeled space radiation) on the musculoskeletal response to exercise countermeasures.

Experiments supporting Specific Aim 1 [does partial weightbearing (~1/6 g) mitigate losses observed with full unloading (~ 0 g)] are just concluding in early June 2009, hence we are not yet able to report on key findings. We have made a "course correction" in the design of those first experiments. To simulate the additional loadbearing incurred by crew members locomoting on the Lunar surface due to the weight of EVA spacesuits, we elected to add one additional group of animals designated "1/3 g" (since current spacesuit design is roughly equivalent to one body weight, hence doubling the load bearing in the 1/6 g environment). This is easily accommodated by our partial g mouse model, since weightbearing can be titrated to whatever fraction of 100% body weight is desired.

We are concurrently preparing to start Experiment 2 (supporting Specific Aim 2: does low-dose radiation exposure change the bone or muscle response to partial gravity). This is a dose-response study utilizing reference x-ray radiation to assess responses of bone and muscle at early (~3 days), "delayed" (~21 days) and "recovery" (~56 days) time points. To achieve the best sensitivity possible, we have added cell culture studies to this experiment at the earlier timepoints to assess the impact on osteoprogenitor cell populations in the marrow. Pilot experiments are in progress to verify our procedures with primary cell culture.

Year 2 of this project will hence start with Experiment 2 (beginning July 2009) utilizing 108 mice (12 groups of 9 each) to test responses at the 3 time points listed above at 3 different radiation exposures. We will choose the lowest radiation dose producing detectable change in muscle protein synthesis and bone formation rate to use in the subsequent Experiment 3, commencing in February 2010, which will test the effects of x-ray exposure on the response to simulated partial gravity; in this experiment, mice subjected to 1/3 g (and weightbearing control mice) will be exposed to one acute dose of x-ray (low LET) radiation as well as 3 fractionated doses. Results of Experiment 2 will also be critical to constructing a beam time proposal for a repetition of Experiment 3 at Brookhaven National Lab during Year 3 of this project.

The project PI (S. Bloomfield) is attending NASA's Space Radiation Summer School at Brookhaven National Laboratory in June 2009. Both the conceptual and practical knowledge gained will prove invaluable for the later preparation of a beam time proposal as well as preparing for the logistics of conducting 3-week long experiments with live animals at the NASA Space Radiation Laboratory facility.

Research Impact/Earth Benefits: Defining the impact of partial weightbearing (as opposed to complete removal of weightbearing) has potentially important implications for rehabilitative strategies applied to stroke or spinal cord-injured patients. Should 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), DOE/nuclear industry workers accumulating occupational exposures, and patients accumulating large exposures with multiple medical procedures.

Task Progress & Bibliography Information FY2009 
Task Progress: The first few months of this project year were dominated by planning activities and interviewing of post-doctoral fellow candidates; an outstanding candidate with 4 years of post-doctoral experience and a rich background in bone biology (Dr. Florence Lima) was successfully hired and joined the lab as of September 1, 2008. Our laboratory hosted a visit by our consultant, Dr. Erika Wagner of MIT, in August of 2008 to train our lab personnel in the logistics of the partial gravity mouse model critical to our specific aims. Multiple pilot experiments in the fall of 2008 confirmed effective doses of fluorochrome labeling (for bone formation rate) and the minimal amount of muscle tissue needed for assessing protein synthesis rates. Experiments supporting Specific Aim 1 (does simulated Lunar gravity protect against those bone and muscle decrements observed with simulated zero gravity) are nearly complete, with the final animals being euthanized the week of June 8, 2009. We added an additional group of animals to simulate the additional loading imposed by EVA spacesuits (approximately doubling effective body weight for an average weight crew member); given that this produces 1/3 body weight (~ 1/3 g), these data will also yield interesting clues about the impact of Martian gravity conditions on musculoskeletal integrity.

While these experiments were still running, work has begun on Specific Aim 2 (determine impact of low-dose radiation exposure on muscle/bone integrity in modeled Lunar gravity); in particular, we have been planning for Experiment 2, the preliminary dose-response experiment with reference x-ray radiation Multiple consultations with other team PIs and with Dr. Marcelo Vasquez (NSBRI HQ) helped us refine our specific exposure doses and time of animal sacrifice relative to exposure day. Our post-doctoral fellow, skilled in primary cell culture work, has added osteoprogenitor cell differentiation and proliferation assays to our outcomes from these experiments. Pilot studies started in May 2008 to confirm viability and lack of contamination of primary cultures derived from mouse bone marrow samples are thus far successful. We plan to begin Experiment 2, testing 3 x-ray exposure doses and three times of sacrifice after exposure, no later than July of 2009.

Bibliography Type: Description: (Last Updated: 05/28/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Hogan HA, Swift JM, Nilsson MI, Bloomfield SA. "Effects of simulated resistive exercise on cortical bone in the tibia mid-diaphysis of hindlimb unloaded rats." 30th Annual Meeting of the American Society of Bone and Mineral Research, Montreal, Canada, September 12-16, 2008.

J Bone Miner Res. 2008 Sep;23 (Suppl 1):S232. , Sep-2008

Abstracts for Journals and Proceedings Swift JM, Bouse SD, Nilsson MI, Bloomfield SA. "High intensity muscle stimulation has an anabolic effect on unweighted tibia and maintains ankle plantar-flexor muscle strength." 2008 APS Intersociety Meeting: The Integrative Biology of Exercise V, Hilton Head, SC, September 24-27, 2008.

2008 APS Intersociety Meeting: The Integrative Biology of Exercise V, Hilton Head, SC, September 24-27, 2008. Meeting Program and Abstracts, p. 40. , Sep-2008

Abstracts for Journals and Proceedings Swift JM, Swift SN, Bloomfield SA. "Beta-adrenergic receptor agonist administration during hindlimb unloading effectively mitigates reductions in cancellous bone formation rate." 30th Annual Meeting of the American Society of Bone and Mineral Research, Montreal, Canada, September 12-16, 2008.

J Bone Miner Res. 2008 Sep;23(Suppl 1):S231. , Sep-2008

Articles in Peer-reviewed Journals Baek K, Barlow AA, Allen MR, Bloomfield SA. "Food restriction and simulated microgravity: effects on bone and serum leptin." J Appl Physiol. 2008 Apr;104(4):1086-93. PMID: 18276897 , Apr-2008
Articles in Peer-reviewed Journals Baek K, Bloomfield SA. "Beta-adrenergic blockade and leptin replacement effectively mitigate disuse bone loss." J Bone Miner Res. 2009 May;24(5):792-9. PMID: 19113907 , May-2009
Articles in Peer-reviewed Journals Prisby RD, Swift JM, Bloomfield SA, Hogan HA, Delp MD. "Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat." J Endocrinol. 2008 Dec;199(3):379-88. PMID: 18755885 , Dec-2008
Articles in Peer-reviewed Journals Swift JM, Nilsson MI, Sumner LR, Jeffery JM, Hogan HA, Bloomfield SA. "Simulated resistance training during hindlimb unloading abolishes disuse bone loss and maintains muscle strength." Journal of Bone and Mineral Research. Submitted, 2009. , Jun-2009
Dissertations and Theses Lucas MW. "A novel method for the evaluation of mechanical properties of cancellous bone in the rat distal femur." Thesis (MS), Texas A&M University, August, 2009. , Aug-2009
Project Title:  Maintaining Musculoskeletal Health in the Lunar Environment Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 05/30/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bloomfield, Susan A. Ph.D. / Texas A&M University 
Address:  Department of Health & Kinesiology 
400 Harvey Mitchell Pkwy, Suite 300 
College Station , TX 77843-4375 
Email: sbloom@tamu.edu 
Phone: 979-845-2871  
Congressional District: 17 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Texas A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Hogan, Harry  Texas A&M University 
Fluckey, James  Texas A&M University 
Braby, Leslie  Texas A&M University 
Project Information: Grant/Contract No. NCC 9-58-MA01602 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-MA01602 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) HHC1:Can partial gravity be simulated on Earth?
(2) HHC2:How does 1/6-g and 3/8-g influence countermeasures?
(3) Osteo04:We do not know the contribution of each risk factor on bone loss and recovery of bone strength, and which factors are the best targets for countermeasure application (IRP Rev E)
Task Description: The overarching purpose of this project is to determine if the usual bone and muscle loss observed during spaceflight will be mitigated by the moon's partial gravity, if radiation exposure exacerbates bone/muscle loss at this reduced loading level, and if exercise is effective in mitigating the loss under these conditions. This requires an effective model of the lunar environment that simulates conditions during lunar outpost missions.

We will use a novel, partial-gravity mouse model to first determine the independent impact of the moons 1/6 gravity on multiple bone and muscle outcomes, including direct determinations of bone breaking strength and other mechanical properties as well as muscle function in the live animal. We will then test the additional impact of low-dose radiation modeling galactic cosmic radiation during partial gravity conditions by exposing these mice to one acute dose, or four, fractionated doses on a weekly basis, of ionizing radiation.

Data from these experiments will be used to justify expanded experiments at the Brookhaven NASA Space Radiation Laboratory utilizing heavy iron ions to simulate galactic cosmic radiation. Finally, we will assess the impact of the lunar environment (partial gravity plus modeled space radiation) on the musculoskeletal response to exercise countermeasures.

Using an animal model to pursue these objectives provides for these advantages:

1. Direct determinations of bone quality with mechanical testing of bone at the end of each experiment;

2. Discovering the effect of radiation on the response to partial gravity and to exercise countermeasures, which cannot be ethically tested in human subjects; and

3. More rapid turn-around and much reduced cost for experiments than those involving long-duration human bed-rest studies.

These experiments will provide unique and valuable data about bone loss and impaired muscle function and determine efficacy of two different exercise countermeasures in a modeled lunar environment.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2008 
Task Progress: New project for FY2008.

Bibliography Type: Description: (Last Updated: 05/28/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2008