# Communication dysfunction in Parkinson disease: Integrated genetic and protein expression analysis of neural pathways to identify treatment targets

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $153,000

## Abstract

Abstract
Individuals with Parkinson disease (PD) experience vocal communication deficits that negatively impact health
and quality of life. PD pathology is widespread, including alpha-synuclein aggregation and decreases in
neurotransmission within brainstem regions. However, very little is known about how these PD-associated
pathologies contribute to vocal communication deficits and thus, current treatments are ineffective. To develop
treatments tailored to vocal dysfunction, it is paramount to understand pathology at gene and protein levels. The
proposed research will address these unknowns by profiling differentially expressed transcripts using RNA
sequencing in brainstem regions linked to vocal production in health and PD. We will use a validated rat model
of PD, Pink1-/-, and compare data to aged-matched wildtype (WT) controls. Pink1-/- rats show early, progressive
vocal communication deficits that recapitulate communication deficits in human PD. Pink1 -/- and WT rats will
be studied at two timepoints, 2 months (prior to deficits) and 8 months (early-stage pathology). Because there
are known sex differences with human PD, we will characterize female vocalizations and correlative pathology.
The proposed work is a series of studies that are an exploratory, descriptive, and hypothesis-driven to
demonstrate associations between vocal behavior, gene expression networks, and consequences on protein
regulation. Specific aims for this proposal are 1A) to identify and compare large-scale gene expression
variations in brainstem regions that regulate vocal communication in Pink1 -/- and WT male and female
rats and 1B) biologically validate vocalization-related modules correlated to individual gene, protein, and
vocal data in Pink1 -/- and WT male and female rats. We hypothesize that male and female Pink1 -/- rats will
show functional vocal deficits compared to WT (Experiment (Exp) 1) and we expect behavioral differences
between male and female rats within both genotypes and between genotypes (Exp 2). We expect vocal
parameters to differ between 2 and 8 months of age for all groups. Further, we expect that Pink1 -/- rats will
demonstrate differential expression of genes involved in neurotransmitter, receptor, and enzyme expression,
homeostatic function, growth factors, synaptic plasticity and transcription factors, as well as key genes
associated with PD pathology in the periaqueductal gray and nucleus ambiguus, but not the non-vocal motor red
nucleus, compared to WT (Exp 3). WCGNA bioinformatics analysis will identify differentially expressed genes
that can be categorized into network modules based on function in Pink1 -/- rats compared to WT (Exp 4).
Finally, we expect that the individual relative mRNA expression (Exp 5) and protein concentrations (Exp 6) will
correlate with the extent of vocal dysfunction. These data will provide insight into novel targets that represent a
direct mechanistic link to vocal deficits in PD. This translational research co...

## Key facts

- **NIH application ID:** 9829097
- **Project number:** 5R21DC016135-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Cynthia A Kelm-Nelson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,000
- **Award type:** 5
- **Project period:** 2017-12-08 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829097

## Citation

> US National Institutes of Health, RePORTER application 9829097, Communication dysfunction in Parkinson disease: Integrated genetic and protein expression analysis of neural pathways to identify treatment targets (5R21DC016135-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9829097. Licensed CC0.

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