# Regeneration  of Auditory Synapses

> **NIH VA I21** · JOHN D DINGELL VA MEDICAL CENTER · 2024 · —

## Abstract

Previous studies showed that blast-exposed and traumatic brain injury (TBI) Veterans had normal hearing
thresholds but exhibited auditory synaptopathy, including central auditory processing deficits and subclinical
levels of hearing dysfunction. In the peripheral auditory system, cochlear synaptopathy is the degeneration of
inner hair cell synapses in the presence of nearly normal audiometric measurements and hair cells, which has
been reported in age-related and noise-induced hearing loss rodent models. Knowledge of central auditory
synaptopathy, however, remains very limited. Currently, the molecular mechanism critical for central auditory
synaptopathy has not been determined, which restricts the understanding of central auditory synaptopathy and
the development of specific treatment methods. Therefore, there is a critical need to study central auditory
synapse and synaptopathy. In this proposal, spiral ganglion neuron-cochlear nucleus (SGN-CN) synapse will be
investigated, as the SGN-CN synapse is the first central auditory relay that receives signals from the inner ear.
Without functional SGN-CN synapses, auditory signals cannot be efficiently transferred to the brain. The
objectives of this proposal are to understand the molecular mechanism critical for SGN-CN synapse integrity
and develop novel therapeutic approaches to treat SGN-CN synaptopathy. Progranulin is a secreted glycoprotein
that is associated with a variety of neuronal activities, including neuronal survival, neurite outgrowth, synapse
formation, neuroinflammation, and neurodegeneration. The role of Progranulin in auditory synapses has not
been reported. Our preliminary data suggest the relationship between Progranulin and SGN-CN synapses.
Based on previous and our preliminary data, we hypothesize that Progranulin may regulate mouse SGN-CN
synapse integrity. To test this hypothesis, we will characterize SGN-CN synaptopathy in the Grn-/- mouse model
and determine the extent to which Progranulin plays a role in young adult mouse SGN-CN synapse integrity
(Aim 1). In Aim 2, we will determine the extent to which Progranulin rescues the structure and function of SCN-
CN synaptopathy. The results of this proposal will significantly advance knowledge in the integrity and
regeneration of auditory synapses, which is a largely understudied VA rehabilitation research area. If cochlear
synaptopathy is found in the Grn-/- mouse in this proposal, we will further characterize the role of Grn in cochlear
synaptopathy and determine whether Grn-/- mouse SGN-CN synaptopathy is primary, secondary, or mixed in our
future proposals. Additionally, we will investigate the role of Grn in age-related and noise-induced auditory
synaptopathy. Outcome of these studies will unravel the molecular mechanisms critical for auditory synaptopathy
and open new avenues to develop specific strategies for the treatment of auditory synaptopathy.

## Key facts

- **NIH application ID:** 10876924
- **Project number:** 5I21RX003866-02
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Zhengqing Hu
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876924

## Citation

> US National Institutes of Health, RePORTER application 10876924, Regeneration  of Auditory Synapses (5I21RX003866-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10876924. Licensed CC0.

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