Thesis
Glucocorticoids modulate aminoglycoside-induced damage to the zebrafish lateral line
Washington State University
Master of Science (MS), Washington State University
2017
Handle:
https://hdl.handle.net/2376/100319
Abstract
Aminoglycoside antibiotics have potent antibacterial properties, but cause hearing loss in up to 25% of patients. These drugs are commonly administered to patients with high glucocorticoid levels, suggestive of patient stress, and can be combined with glucocorticoid treatment, yet the interaction of glucocorticoids and hearing loss has not been explored. In this study, we investigated the effect of the natural glucocorticoid stress hormone cortisol or the synthetic glucocorticoid dexamethasone on hair cells in the zebrafish lateral line as a step in understanding how glucocorticoids modulate hair cell survival. The lateral line is a system of hair cells stereotypically located along the exterior of fish that is used to detect local changes in fluid dynamics for behaviors such as predator avoidance and prey detection. Using this system, we tested the hypothesis that glucocorticoids can modulate hair cell sensitivity to aminoglycosides. We found that overnight incubation in the natural glucocorticoid cortisol sensitized hair cells to neomycin damage, and that sensitization depended on the action of both the glucocorticoid receptor and the mineralocorticoid receptor. By contrast, 3-day incubation in the synthetic glucocorticoid dexamethasone may confer protection against aminoglycoside damage. We also found that the cortisol treatment increased internal cortisol levels and glucocorticoid transcriptional activity in whole fish, and saw evidence for glucocorticoid transcriptional activity in cortisol-treated hair cells. Collectively, our results suggest that the natural glucocorticoid cortisol interacts with neomycin-induced damage to hair cells to increase hair cell death through action of the glucocorticoid and mineralocorticoid receptor, likely via a genomic mechanism. Overall, our work shows that different glucocorticoids can have distinct effects on aminoglycoside damage to hair cells. The variability across and within our experiments highlights the importance of practicing appreciation for the complexity and variability of glucocorticoid signaling during study design, implementation, and interpretation.
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Details
- Title
- Glucocorticoids modulate aminoglycoside-induced damage to the zebrafish lateral line
- Creators
- Tamasen Fern Hayward
- Contributors
- Allison B. Coffin (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Biological Sciences, School of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525102901842
- Language
- English
- Resource Type
- Thesis