Browsing by Subject "hindlimb unloading"
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Item Osteogenic effect of optimized muscle stimulation exercise as a countermeasure during hindlimb unloading(2009-05-15) Sumner, Lindsay RebeccaItem Simulated Microgravity and Radiation Exposure Effects on the Regulation of Skeletal Muscle Protein Synthesis(2012-10-19) Wiggs, MichaelLong duration spaceflight missions out of lower earth orbit, back to the lunar surface, or possibly to Mars highlight the importance of preserving muscle mass and function. Muscle atrophy occurs within days of exposure to microgravity and prevailing thought is that a primary mechanism for muscle atrophy is a reduction in skeletal muscle protein synthesis. This dissertation examines the ability of skeletal muscle to recover muscle protein synthesis with slight perturbation, such as ambulatory reloading during disuse as well as partial loading, similar to body mass seen on the moon or Mars. We use traditional precursor-product labeling to measure protein synthesis, but use a relatively novel tracer, deuterium oxide, in order to make cumulative measures of protein synthesis over 24 h. The overarching goal of this dissertation is to define the response of skeletal muscle protein synthesis to different loading parameters in order to better understand the contribution of protein synthesis to skeletal muscle mass during disuse. In the first study, we demonstrate that muscle atrophy during 5 days of hindlimb unloading is in part due to a decrease in protein synthesis. We also highlight the ability of skeletal muscle to adapt by allowing two 1 h ambulatory reloading sessions on days 2 and 4. Although this countermeasure is able to rescue protein synthesis in soleus and gastrocnemius, it is unable attenuate any losses in muscle mass. In the second study, we compare partial weight loading to traditional hindlimb unloading. Weight bearing of 1/3 or 1/6 body weight is able to attenuate losses in muscle mass seen with unloading. Protein synthesis is maintained after 21 days of the experimental protocol, suggesting that protein synthesis is responsive to load and is likely not the only mechanism for determining muscle mass. In the final study, the effects of < 1 Gy x-ray exposure and partial weight suspension are measured to better understand the complex space environment, which includes a wide variety of radiation. Surprisingly, we found no effects of radiation on muscle protein synthesis in 1 G or partial loading. Targeting only protein synthesis may not be enough of a stimulus as evidenced by the data in this dissertation. Future plans should use a multiple-systems approach to counteract atrophy by increasing protein synthesis to maintain/elevate muscle mass during periods when it is otherwise compromised.Item Skeletal Response to Simulated Microgravity Exposures and Exercise in the Adult Rat Model(2013-04-29) Shirazi-Fard, YasamanMechanical unloading has deleterious effects on the musculoskeletal system and results in significant reductions in bone density, mass, and strength, which do not fully recover even years after returning to weightbearing. For example, the rate of bone loss in microgravity is 10-fold more rapid than the rate of loss seen in elderly Caucasian females, the population group most predisposed to osteoporosis. This raises concern with individuals who are exposed to multiple bed rest periods or crewmembers who make repeated missions. Exercise offers a way to reduce or reverse these effects. Dual-energy X-ray absorptiometry (DXA) densitometry and bone mineral density (BMD) alone are generally insufficient for capturing the complex changes in bone mass, structure, and integrity and not an accurate predictor of fracture risk. Therefore, it is essential to measure the mechanical properties of bone tissue directly using animal models. The hindlimb unloaded (HU) rat model is a well-established ground-based analog for studying bone response to disuse and effects of spaceflight. The current study is one of the very few that has measured longitudinally densitometric and mechanical properties of bone after repeated simulated microgravity and long-term recovery at multiple anatomic sites in skeletally mature rats. The specific aims were to characterize 1) loss and recovery dynamics of bone following a period of unloading, 2) bone response after a second exposure to 28 days of HU, following an initial 28 days of HU and a recovery period equal to twice the duration of initial exposure, and 3) effects of resistance exercise during recovery period following an initial HU exposure and its effects on a subsequent exposure. In general, our data showed that bone response to unloading and recovery is site-specific. More specifically, we found that: 1) the rat proximal tibia metaphysis modeled the loss and discordant recovery dynamics as seen in the International Space Station (ISS) crewmembers proximal femur better than the rat femoral neck; 2) the initial exposure to HU has minimal effect on the subsequent HU exposure, and detrimental effects of the second HU exposure were milder than the initial due to reduced mechanosensitivity of the bone; 3) exercise significantly enhanced recovery following the initial HU exposure, and losses during the second exposure were not affected by exercise in most cases.Item The Effects of Multiple Unloading Exposures on Bone Properties in the Femur of Adult Male Rats(2012-07-16) Morgan, Derrick ScottNASA goals include long-term International Space Station (ISS) missions and the ambitious objective of eventually sending astronauts to Mars. Unfortunately, exposure to unloading due to microgravity during spaceflight has been shown to cause detrimental health effects on bone. Therefore, NASA is seeking a ground-based animal model to study the long-term effects of unloading on bone in order to better insure the health and mission capability of astronauts. The hindlimb unloaded (HU) rat model was used to study the effects of multiple unloading exposures and aging on bone properties. Six month old, adult, male Sprague-Dawley rats were separated into the following groups: baseline (BL, sacrificed when received at 6 months age), aging cage control (AC, normal weight-bearing cage activity), 1HU7 (unloaded for 1 month starting at 7 months of age and allowed to recover for 3 months), 1HU10 (normal cage activity until 10 months of age, unloaded for 1 month, recovered for 2 months), and 2HU10 (unloaded for 1 month at 7 months of age, allowed to recover for 2 months, unloaded again for 1 month at 10 months of age, followed by 2 months of recovery). Every 28 days a subset of animals (n=15) were euthanized and both femurs were excised. A peripheral quantitative computed tomography (pQCT) scanner was used to collect densitometric and geometric properties at the right and left femoral neck and at the left femoral midshaft. Mechanical testing (axial and lateral compression of the femoral neck and 3pt bending of the midshaft) was performed at each location and strength indices based on pQCT parameters were calculated. Femoral neck properties decreased due to HU but recovered with respect to increase over HU, BL, and AC by the end of the recovery periods. Femoral midshaft properties were relatively unaffected, but did show slight decreases for older animals at month 10, which recovered during the two month recovery period. Femoral neck geometry exhibited increased endocortical resorption and periosteal apposition of the cortical shell which suggests that trabecular bone plays an important role in how the total bone is affected by HU. Densitometric properties were affected less by HU with respect to BL than were mechanical strength values. Results suggest that femoral neck is more affected by unloading than midshaft, particularly for multiple exposures of unloading. Also, aging does not appear to be a critical factor for bone loss due to HU for either femoral neck or midshaft.