# Pathways, mechanisms, and treatments of vocal communication deficits in a Parkinson rat model

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $333,631

## Abstract

PROJECT SUMMARY/ABSTRACT
Greater than 90% of individuals with Parkinson disease (PD) experience significant vocal communication
deficits that appear early in the manifestation of the disease, negatively impact quality of life, and are refractory
to current therapeutic approaches. PD pathology occurs in both the central and peripheral nervous systems
and differs according to sex, but how this affects vocal communication is unknown and presents a critical gap
in knowledge, limiting current patient treatments. This research will elucidate how vocal dysfunction manifests
at a biological and functional level. The long-term goal and primary objective of this work is to understand,
prevent, and/or reverse vocal communication deficits in individuals with PD. To accomplish this, a validated rat
model of PD, Pink1-/-, will be used. Male and female Pink1-/- rats show early, progressive vocal deficits with
brainstem and laryngeal pathology that recapitulate the communication deficits observed in human PD. Based
on preliminary data, this research will address the hypothesis that the neuroanatomical biochemistry of
vocalization pathways in Pink1-/- rats is significantly different compared to wildtype control rats
(Specific Aim 1). The rationale for this study is the need for basic, mechanistic information on sex-specific
vocal pathways and respective connections that will be key targets to improve and/or modulate vocal behavior
over time. By applying retrograde tracers into the vocal fold, the peripheral (larynx) to central (brainstem)
connections will be assessed in Pink1-/- and control rats. Using 3D modeling, differences in the distribution and
density of neurons within central nervous system vocalization pathways will be quantified. Because current
treatments for PD voice deficits are insufficient, the second goal of this proposal is to address the hypothesis
that currently approved therapeutics will be identified and validated for the treatment and modulation
of PD vocal communication deficits (Specific Aim 2). The rationale for this work is the need for drugs that
effectively modulate vocal production for future human PD clinical trials. Using gene targets from Pink1-/-
larynx and brainstem datasets, a list of biologically relevant drugs will be generated using drug-repurposing
catalogs. The application of selected drugs to in vitro Pink1-/- larynx as well as brainstem cell cultures will
generate significant alterations in the gene transcript as quantified with single cell RNA-sequencing. To confirm
efficacy, these therapeutics will be administered to Pink1-/- rats to measure in vivo vocalization improvements.
The simultaneous administration of new drugs to both biological (cellular) and functional (animal) platforms
provides distinct yet integrated information that is unable to be obtained from the human patient population.
This approach is innovative because it incorporates new techniques and theory from molecular, physiological,
and communication scie...

## Key facts

- **NIH application ID:** 10028358
- **Project number:** 1R01NS117469-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Cynthia A Kelm-Nelson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $333,631
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028358

## Citation

> US National Institutes of Health, RePORTER application 10028358, Pathways, mechanisms, and treatments of vocal communication deficits in a Parkinson rat model (1R01NS117469-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10028358. Licensed CC0.

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