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NIH grant 1IK1RD002600-01: Noise exposure-induced myelin degeneration in hearing impariment
Institute: {'code': 'VA', 'abbreviation': 'VA', 'name': 'Veterans Affairs', 'admin_org_id': '12500964', 'admin_funding_url': ''}. PI: Emily Marie Fabrizio-Stover. Award: $.
Start: 2026-10-01T00:00:00.
Significance to VA: Noise-induced hearing loss (NIHL) is one of the most common service-related disabilities
among Veterans. Veterans that perform normally on hearing tests can still exhibit difficulties recognizing
speech, especially in noisy listening conditions. Hearing loss and poor speech recognition are associated with
depression, social isolation, and post-traumatic stress disorder, negatively impacting quality of life. Increasing
evidence suggests that suprathreshold auditory processing is important for speech recognition. However, how
noise-induced pathology contributes to suprathreshold auditory deficits is not well understood. Myelin integrity
in the auditory system is essential for temporal precision and neural synchrony, necessary for encoding
complex auditory stimuli such as speech. We have previously shown that noise exposure can cause myelin
degeneration in the peripheral auditory nerve (AN). However, the effect of noise-induced myelin degeneration
on neural synchrony and the effect of noise exposure on myelin integrity in central auditory regions, important
for speech processing, are unknown. Innovation and Impact: This project would have significant positive
impact by identifying myelin pathology as a novel source of auditory dysfunction after noise exposure, resulting
in the possible development of new diagnostic tools and interventions for noise exposed Veterans.
Furthermore, this proposal will examine the understudied effect of noise exposure on myelin integrity in the
central auditory system. Specific Aims: The long-term goal is to understand the pathophysiology of NIHL to
facilitate the development of diagnostic tools and novel treatments for Veterans with hearing loss and poor
speech recognition after noise exposure. To achieve this, we will use well-established mouse models to test
the following: 1) Aim 1 will test the hypothesis that noise-induced myelin degeneration in the AN is associated
with neural synchrony deficits. 2) Aim 2 will test the hypothesis that noise-exposure induces myelin
degeneration in the central auditory system with concurrent deficits in neural synchrony. Methodology: We will
use a mouse model of noise exposure in young adult CBA/CaJ mice to determine the relationship between
structural measurements of myelin integrity and functional measurements of neural synchrony in the AN (Aim
1), brainstem (Aim 2), and cortex (Aim 2). Structural measurements will utilize supra-resolution
immunohistochemistry imaging of myelin components in each region. Functional measurements will be derived
from electroencephalogram (EEG) measurements of auditory activity for each region of interest. As noise
exposure can result in diverse pathologies in the AN, the same measures will be made in a mouse model of
myelin-only degeneration (QKIFL/FL:PLP-CreERT mice) to determine the specific relationship between myelin loss
and reduced neural synchrony. Path to Translation and Implementation: This study would lead to a better
understanding of the role of myelin dysfunction in noise-induced auditory dysfunction, leading to new
diagnostic tools and therapeutic targets for noise-exposed Veterans. The functional measurements used in this
study are highly translational, ensuring that future studies can examine these relationships directly in Veteran
populations. Career Goals: The immediate career goal is to collect strong preliminary data for a translational
CDA-2 application utilizing auditory evoked electrophysiology in animal models and Veterans. The long-term
career goal is to become an independent investigator focusing on the application of translational research to
understand the pathophysiology of noise-induced auditory dysfunction and develop interventions to improve
hearing outcomes after noise exposure. The key elements of the career plan are designed to support the
applicant’s current and future research proposals and career development. These include: increasing
knowledge of glial and auditory system cell biology, gaining experience in supra-resolution imaging techniques,
learning translational approaches for auditory evoked potential recording, and professional development with
the support of a strong mentoring team.document fetched 2026-10-24 02:46