# DEIA supplement - Myelination Deficits Underlying Auditory Issues in Fragile X Syndrome

> **NIH NIH R15** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2022 · $437,653

## Abstract

Project Summary:
Autism spectrum disorder is characterized by an inability to function in environments with multiple competing
sound sources, such as noisy classroom. These auditory issues likely originate early in sound location
processing that occurs in the brainstem. The projections that make up the auditory brainstem circuit that
processes binaural (information from both ears), temporal, and intensity differences are dependent on heavily
myelinated axons that convey this very precise information accurately from the cochlea to the brain. Our
preliminary data shows that auditory brainstem axons are smaller in diameter and thinner in Fragile X
Syndrome mice, a monogenetic form of autism. Additionally, we see a decrease in the latency of binaural
waves in the auditory brainstem response (ABR), a non-invasive electrophysiological recording of this circuit, in
FXS mice compared to controls. Lastly, we see increased latencies to respond to reflexive auditory behavioral
stimuli in FXS mice compared to controls. These data suggest that myelination deficits may underly binaural
hearing difficulties in FXS, and perhaps ASD. We propose to further characterize myelination deficits in FXS
mice using anatomical, physiological, and behavioral measures of myelination (immunohistochemistry/lipid
measurements, ABRs, and prepulse inhibition of the acoustic startle response) to determine the mechanisms
underlying myelination issues in FXS across developmental timepoints. Additionally, we aim to determine the
dependence of myelination deficits on the presence of Fragile X Mental Retardation Protein (FMRP), the
protein lacking in FXS, by reintroducing FMRP through adeno-associated viruses (AAVs) expressing FMRP
during development. Results from this study will determine how myelination contributes to binaural hearing
processing issues in FXS and whether these deficits are rescued by re-expression of FMRP. All the above-
mentioned experiments are approachable for undergraduate researchers thus funding from NIH will further
broaden participation of students in biomedical research and increasing student’s knowledge and ability to
conduct basic research.

## Key facts

- **NIH application ID:** 10605699
- **Project number:** 3R15HD105231-01S1
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** Elizabeth Anne McCullagh
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $437,653
- **Award type:** 3
- **Project period:** 2021-09-09 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10605699

## Citation

> US National Institutes of Health, RePORTER application 10605699, DEIA supplement - Myelination Deficits Underlying Auditory Issues in Fragile X Syndrome (3R15HD105231-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10605699. Licensed CC0.

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