# The Role of Vesicular Zinc in Noise-induced Cochlear Degeneration and Hearing Loss

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $45,520

## Abstract

Project Summary/Abstract
Exposure to loud noise causes degeneration in the cochlea involving hair cell death and ribbon synapse loss,
resulting in permanent deficits that can be hidden or overt. The exact mechanisms by which noise-induced
hearing loss occurs are not clear, and there is a need to identify the critical events that result in permanent
cochlear degeneration. Vesicular zinc is important in the nervous system in fine-tuning synaptic transmission
and sound processing, but in cases of nervous system injury, such as in the retina, vesicular zinc exacerbates
neurodegeneration and hinders regeneration. Our preliminary audiometric and histological data indicate that
removal of vesicular zinc via genetic deletion of ZnT3, the vesicular zinc transporter loading zinc in presynaptic
terminals, results in resilience to- and improved recovery from noise-induced hearing loss, both in terms of
structure and function. Furthermore, both cochlear and systemic chelation of zinc result in resilience to noise-
induced hearing loss. Moreover, ZnT3 protein expression increases immediately following noise exposure,
consistent with a role for vesicular zinc dysregulation in noise-induced hearing loss. This proposal aims to test
the hypothesis that noise-induced dysregulation of zinc signaling contributes to noise-induced hearing loss by
promoting degeneration and limiting regeneration in the cochlea. Using a combination of cochlear physiological
recordings, histological analysis, and quantitative protein and RNA analysis, this proposal will examine the
effects of vesicular zinc following harmful noise exposure. Results from this proposal will help to elucidate the
mechanisms of degeneration within the cochlea that lead to temporary and permanent hearing impairments after
noise-induced hearing loss. These data may provide novel therapeutic targets for treatment of noise-induced
hearing loss and related disorders, such as tinnitus and hyperacusis, and further our understanding of cochlear
vulnerability to noise.

## Key facts

- **NIH application ID:** 10152266
- **Project number:** 1F31DC019027-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Brandon Bizup
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-09-04 → 2023-09-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152266

## Citation

> US National Institutes of Health, RePORTER application 10152266, The Role of Vesicular Zinc in Noise-induced Cochlear Degeneration and Hearing Loss (1F31DC019027-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10152266. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*