# Role of the Innate Immune System in the Survival of Auditory Neurons

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $591,548

## Abstract

Spiral ganglion neurons transmit auditory information from cochlear hair cells to the neurons of the cochlear
nucleus. Thus, spiral ganglion and cochlear nucleus neurons are essential for normal hearing and for
restoration of hearing via cochlear or cochlear nucleus implants in deaf individuals. However, in some
circumstances these neurons may degenerate or die after deafening, limiting the potential efficacy of these
devices. The reasons for this neurodegeneration and its variable nature after hair cell death remain unclear.
Recent findings from our labs have revealed that elements of the innate immune system are recruited to the
spiral ganglion and cochlear nucleus after deafening and suggest that the activation status of immune cells is
an important determinant of neuronal survival in both structures. We also show that these elements of the
innate immune system have profound effects on the survival of the auditory neurons, in some cases being
cytotoxic, in others possibly neuroprotective. In at least one deafness model, the immune response,
remarkably, may be a principal cause of spiral ganglion neuronal death after deafening. To resolve these
complex and disparate effects of the innate immune system on auditory neuronal survival – with the long-term
goal of developing immunotherapies for neuroprotection – we propose to systematically delete specific
components of the innate immune system involving Natural Killer (NK) cells, macrophages, or microglia to
determine their effect on neuronal survival. The experiments will use transgenic mice and, in some cases,
inhibitory antibodies. Both macrophages and NK cells are recruited into the spiral ganglion in response to hair
cell injury. The proposed experiments will determine whether macrophages and NK cells are neurotoxic or
neuroprotective in the injured cochlea and the roles of specific cytokines and chemokines in stimulation and
potential neurotoxicity of these immune cells. A parallel series of studies will focus on neuroimmune
interactions in the cochlear nucleus, in which extensive research by one of the co-PI's has shown that neuronal
survival depends on afferent input during a `critical period' in early postnatal maturation. In contrast, mature
cochlear nucleus neurons survive deafferentation. Preliminary data suggest that this may be due to
neuroprotection by microglia (the resident immune cells of the CNS.) The proposed experiments will test this
hypothesis. Together, these studies will test fundamentally new hypotheses implicating specific components of
the innate immune system as critical, if not optimal, targets for neuroprotective therapies to promote survival of
cochlea and auditory brainstem neurons after cochlear pathology.

## Key facts

- **NIH application ID:** 10183216
- **Project number:** 5R01DC015790-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** STEVEN H GREEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $591,548
- **Award type:** 5
- **Project period:** 2017-07-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183216

## Citation

> US National Institutes of Health, RePORTER application 10183216, Role of the Innate Immune System in the Survival of Auditory Neurons (5R01DC015790-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10183216. Licensed CC0.

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