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dc.contributor.authorBaranowski, Ryan
dc.date.accessioned2022-09-15T17:48:14Z
dc.date.available2022-09-15T17:48:14Z
dc.identifier.urihttp://hdl.handle.net/10464/16595
dc.description.abstractProlonged microgravity exposure causes muscle atrophy and fiber type transformations from a slow oxidative to the fast glycolytic phenotype. Glycogen synthase kinase-3 (GSK3) is a serine/threonine kinase and known negative regulator of NFAT and Wnt/β-catenin signaling. Together, NFAT and Wnt/β-catenin signaling pathways can activate the slow-oxidative myogenic program and muscle regeneration. Part 1 of this thesis examined soleus muscles from male and female C57BL/6 mice from three separate missions (NASA RR9 [male, n=10 per group, 35 days in space], NASA RR1[female, n=4 per group, 37 days in space], BION-M1 [male, n=4 per group, 30 days in space]) to examine GSK3 activation via western blotting. I examined total and inhibitory serine9 phosphorylated GSK3 and β-catenin content in Flight, Ground Control (GC) and Vivarium control (VIV) soleus muscles. I found that ~1 month of spaceflight led to significant reductions in total GSK3. Changes in serine9 phosphorylated GSK3 varied across missions. When examining β-catenin, we found that the RR9 group showed a significant reduction in the flight group compared with GC and VIV. We also showed a collective slow-to-fast fibre type shift via MHC analysis. Part 2 of this thesis examined the effects of muscle-specific GSK3 knockdown (GSK3mKD) in male mice during hindlimb suspension (HLS) – a simulated model of microgravity. Through western blot analysis we showed a 50% reduction of GSK3 in soleus muscles from GSK3mKD mice. After subjecting the mice to 7 days of HLS, DXA analysis showed that GSK3mKD mice maintained body weight throughout the 7 days and had more lean mass compared to GSK3flox control mice. Additionally, soleus muscles from GSK3mKD mice had greater soleus muscle mass and cross-sectional area after HLS compared with GSK3flox HLS mice; and force production was not different from mobile control GSK3flox mice. Together my thesis found that GSK3 content was consistently reduced in soleus muscles from spaceflight, and that muscle specific GSK3 knockdown can increase soleus muscle size and force production.en_US
dc.language.isoengen_US
dc.publisherBrock Universityen_US
dc.subjectGSK3en_US
dc.subjectSkeletal Muscleen_US
dc.subjectSpaceflighten_US
dc.titleExploring the role of glycogen synthase kinase 3 in murine soleus unloading with real and simulated microgravityen_US
dc.typeElectronic Thesis or Dissertationen
dc.degree.nameM.Sc. Applied Health Sciencesen_US
dc.degree.levelMastersen_US
dc.contributor.departmentApplied Health Sciences Programen_US
dc.degree.disciplineFaculty of Applied Health Sciencesen_US
refterms.dateFOA2022-09-15T00:00:00Z


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