Year of Publication

2020

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department

Physiology

First Advisor

Dr. Gregory I. Frolenkov

Abstract

The rigid, paracrystalline actin core of auditory hair cell stereocilia is extremely stable and after initial formation must persist for the life of the cell to preserve hearing in mammals. In healthy hair cells, turnover of actin molecules occurs only in a small region near the tips of stereocilia, while the actin filaments of the shaft are stable. For decades damage to the actin core of stereocilia from acoustic trauma has only been attributed to cases of permanent noise-induced hearing loss. Here, we show that repairable actin core damage occurs in temporary noise-induced hearing loss from moderate acoustic trauma.

We have found that moderate noise exposure causing a temporary hearing loss results in damage to the stereocilia actin core in the form of small, submicron breaks in the filamentous actin (F-actin) at the base of the stereocilia, and displacement of the stereocilia from its anchoring rootlet. The same damages were recapitulated in vitro after mechanical overstimulation of stereocilia bundles by fluid-jet. Despite the well-established stable nature of the F-actin within stereocilia, 24 hours after the damage we observed complete repair of this damage in vitro and only partial repair in vivo, indicating slower in vivo recovery. The mechanism of this repair appears to involve actin remodeling in the upper portion of the rootlet located within the stereocilia shaft.

Our results suggest that repairable damage to the F-actin at the base of stereocilia is a novel component of temporary noise-induced hearing loss. We believe that restoration of hearing thresholds after moderate noise exposure includes the repair of this damage. Although the exact mechanism of this repair is unknown, this is the first evidence for actin cytoskeleton repair in the stereocilia of auditory hair cells which have to maintain their structure and mechanosensitivity throughout the life of an organism.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2020.410

Funding Information

This research was funded (2012 - 2020) by the National Institutes of Health: National Institute on Deafness and other Communication Disorders grant R01DC014658.

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