THE MUSCLE UNITS OF CAT TIBIALIS POSTERIOR: CLASSIFICATION BASED ON UNIT NEUROMECHANICAL PROPERTIES AND WHOLE MUSCLE HISTOCHEMISTRY
AuthorMcDonagh, Jennifer Crockett
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Degree ProgramGraduate College
Degree GrantorUniversity of Arizona
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Expressing a Z-disk nebulin fragment in nebulin-deficient mouse muscle: effects on muscle structure and functionLi, Frank; Kolb, Justin; Crudele, Julie; Tonino, Paola; Hourani, Zaynab; Smith, John E; Chamberlain, Jeffrey S; Granzier, Henk; Univ Arizona, Dept Cellular & Mol Med (BMC, 2020-01-28)Background Nebulin is a critical thin filament-binding protein that spans from the Z-disk of the skeletal muscle sarcomere to near the pointed end of the thin filament. Its massive size and actin-binding property allows it to provide the thin filaments with structural and regulatory support. When this protein is lost, nemaline myopathy occurs. Nemaline myopathy causes severe muscle weakness as well as structural defects on a sarcomeric level. There is no known cure for this disease. Methods We studied whether sarcomeric structure and function can be improved by introducing nebulin's Z-disk region into a nebulin-deficient mouse model (Neb cKO) through adeno-associated viral (AAV) vector therapy. Following this treatment, the structural and functional characteristics of both vehicle-treated and AAV-treated Neb cKO and control muscles were studied. Results Intramuscular injection of this AAV construct resulted in a successful expression of the Z-disk fragment within the target muscles. This expression was significantly higher in Neb cKO mice than control mice. Analysis of protein expression revealed that the nebulin fragment was localized exclusively to the Z-disks and that Neb cKO expressed the nebulin fragment at levels comparable to the level of full-length nebulin in control mice. Additionally, the Z-disk fragment displaced full-length nebulin in control mice, resulting in nemaline rod body formation and a worsening of muscle function. Neb cKO mice experienced a slight functional benefit from the AAV treatment, with a small increase in force and fatigue resistance. Disease progression was also slowed as indicated by improved muscle structure and myosin isoform expression. Conclusions This study reveals that nebulin fragments are well-received by nebulin-deficient mouse muscles and that limited functional benefits are achievable.
Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle functionHall, Arielle; Fontelonga, Tatiana; Wright, Alec; Bugda Gwilt, Katlynn; Widrick, Jeffrey; Pasut, Alessandra; Villa, Francesco; Miranti, Cynthia K; Gibbs, Devin; Jiang, Evan; et al. (BMC, 2020-11-27)Expression of CD82 is important to sustain satellite cell activation, as in its absence there is decreased cell proliferation and less efficient repair of injured muscle. Loss of CD82 in dystrophic muscle leads to a worsened phenotype compared to control dystrophic mice, with decreased pulmonary function, myofiber size, and muscle strength. Mechanistically, decreased myofiber size in CD82-/- dystrophic mice is not due to altered PTEN/AKT signaling, although increased phosphorylation of mTOR at Ser2448 was observed.
Effects Of Six Weeks Inspiratory Muscle Strength Training On Respiratory Muscle ElectromyographyBailey, E. Fiona; Snell, Eric Wyatt (The University of Arizona., 2019)Inspiratory muscle strength training (IMST) holds promise as a non-pharmacologic treatment that can improve respiratory muscle strength and reduce blood pressure in hypertensive adults. There is a gap in knowledge regarding the specific respiratory mechanisms that gives rise to these favorable outcomes. Here, I explore the effect of IMST on respiratory muscle fatigue, blood pressure, and heart rate in recreationally active men and women. Four subjects underwent a 6-week intervention comprising 30 breaths a day 5 days a week with a respiratory muscle fatigue protocol pre and post intervention. Pre-post intervention measures consisted of resting blood pressure, heart rate, and surface electromyographic (EMG) recordings of the scalene, parasternal, and oblique muscles. The effects of 6 weeks IMST on respiratory muscle fatigue were evaluated in the context of a fatigue protocol and by assessment of the centroid frequency of EMG power spectrum. My preliminary results in 4 subjects failed to show definitive results. I hypothesize that confounding factors, namely individualized breathing strategies contributed considerable variation to the patterns of respiratory muscle activation exhibited by our participants and invalidating pre-post comparisons of EMG power. Future studies should control for breathing patterns within subjects (i.e. across pre-post fatigue protocols) to ensure consistent patterns of respiratory muscle activation. Additionally, care should be taken to ensure uniformity of instructions across both fatigue protocols and daily IMST i.e., use of a diaphragmatic breathing pattern, to minimize between subject differences in respiratory muscle activation.