Date of Award

8-2020

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

Advisor

Clarissa A Henry

Second Committee Member

Gregory Cox

Third Committee Member

Thane Fremouw

Additional Committee Members

Roger Sher

Calvin Vary

Abstract

Skeletal muscle plasticity is imperative for functional adaptation to changing demands in activity. Although a great deal is known about the structural and functional plasticity of healthy skeletal muscle, far less is known about plasticity in diseased muscle. Here, we combined the power of the zebrafish model with the adaptability of neuromuscular electrical stimulation (NMES) to study the basic mechanisms of plasticity in the zebrafish model of Duchenne Muscular Dystrophy (DMD). Four NMES paradigms, defined by their frequency, delay, and voltage, were designed to emulate the repetition and load schemes of human resistance training programs. Additionally, two inactivity paradigms were designed to emulate activity patterns in individuals with DMD. Three sessions of endurance NMES improve muscle structure, increase swim velocity and distance traveled, and extend survival. Endurance NMES significantly increased the number and length of branching for neuromuscular junctions. Nuclear surface area and volume also significantly increased following endurance NMES. Time-lapse imaging suggests less degeneration and improved regeneration of the fast-twitch muscle fibers. Conversely, three days of inactivity worsen muscle structure and decreases survival. Strikingly, inactivity followed by a single session of endurance or power NMES obliterates muscle resilience. Therefore, our data clearly indicate that, at least in the zebrafish model, some resistance training is beneficial whereas inactivity is deleterious for dystrophic muscle. More importantly, though, our data provide a new methodology with which to study muscle plasticity in healthy and diseased muscle.

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