Access Type
Open Access Dissertation
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Physiology
First Advisor
Robert Wessells
Abstract
Exercise is a known, beneficial treatment for a variety of normal (aging) and abnormal (disease) declines in health. These benefits can be observed in a range of tissues, including the brain and muscle, and organelles, such as the mitochondria. Many of the mechanisms through which exercise can promote health in these contexts have recently come to light. However, how these mechanisms can be targeted to promote health in sedentary populations is still under investigation. In Drosophila, stimulation of octopaminergic neurons provides the benefits of endurance exercise to sedentary flies. Neuroplasticity following exercise is one possible mechanism for how octopaminergic activation may promote these benefits, and this possibility is addressed here. Additionally, exercise-induced improvements to health are not universal, and can be hard to attain for some individuals. The same phenomena can be seen in disease states, where genetic variation between individuals can influence disease severity and efficacy of treatment. The generation of model organisms to study disease, and to diversify the testing of therapeutic strategies, is necessary to further our understanding of disease progression and the development of targeted treatments, as well as the influence of genetic background on those treatments. Here, Drosophila models of two rare, progressive diseases, Barth Syndrome and Spinal and Bulbar Muscular Atrophy, are generated and characterized in depth to be used as valuable resources for their respective fields. For Barth Syndrome, we examine the role of genetic background on disease phenotypes such as endurance, mobility, and mitochondrial respiration. Additionally, our newly developed Drosophila models Spinal and Bulbar Muscular Atrophy support a role for both neurons and muscle for targeted treatment of disease phenotypes.
Recommended Citation
Richardson, Kristin Ann, "Chronic Exercise And The Treatment Of Progressive Disorders" (2023). Wayne State University Dissertations. 3876.
https://digitalcommons.wayne.edu/oa_dissertations/3876