Date of Award
Level of Access Assigned by Author
Master of Science (MS)
Second Committee Member
Third Committee Member
Acute or chronic ethanol (EtOH) exposure has been associated with multiple syndromes ranging from the fetal alcohol spectrum disorders to adult-onset neuropathy, myopathy, and respiratory and organ failure. Many symptoms of these disorders, such as poor coordination, poor tandem gait, cramping, and weakness have been attributed to neuropathy, but it has become increasingly clear that EtOH targets muscle tissue as well. In order to gain a comprehensive understanding of EtOH-induced diseases, both the nervous system and skeletal musculature must be studied. Zebrafish have become a prevalent model organism for studying these diseases because it is easy to expose zebrafish to EtOH via their aqueous environment, and their musculature is genetically and structurally similar to humans. Here we used zebrafish as a model to study the effects of EtOH exposure on late-stage embryonic development. We demonstrate that exposure to 2% EtOH at 24, 30, 36 or 48 hours post-fertilization results in myofibers detaching from the myotendinous junction and degenerating, a symptom similar to the fiber detachments associated with congenital muscular dystrophy (CMD). However, these results were variable, which is characteristic of many syndromes associated with EtOH exposure and presents challenges to elucidating a mechanism behind this phenomenon. Although the phenotype is similar to what is seen in CMD, overexpressing paxillin, a gene that has been shown to ameliorate the fiber detachment phenotype in a zebrafish model of CMD, did not rescue fiber detachments induced by exposure to 2% EtOH. We also demonstrated that Evans blue dye, a membrane impermeable dye, permeates myofibers that have degenerated in response to EtOH treatment. Furthermore, β-dystroglycan, a transmembrane protein that is part of a glycoprotein adhesion complex, does not migrate with detached fibers. Although the mechanism behind EtOH-induced fiber detachments is still unknown, these data show that the disruption is occurring within the myofibers and not on the extracellular side of the muscle adhesion complex. Despite the variability we saw in our results, elucidating a mechanism for EtOH-induced myofiber detachment and degeneration could contribute to our overall understanding of EtOH-associated diseases and lead to potential therapies in the future.
Pasquarella, Margaret E., "Investigating Zebrafish (Danio rerio) as a Model to Study Ethanol Toxicity on Muscle" (2017). Electronic Theses and Dissertations. 2777.