# Development of a behavioral rat model to assess proteomic and metabolomic adaptations of laryngeal muscles in response to vocal exercise

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $169,500

## Abstract

Project Summary/Abstract
The development of large-scale, biochemical proteomics and metabolomics approaches has led to a more
sophisticated understanding of the pathways and biomarkers involved in neuromuscular plasticity in response
to use, disuse, and aging in the limb musculature. The laryngeal muscle proteome and metabolome, however,
remain relatively unexplored. Without direct study of the laryngeal muscles, diagnostic and therapeutic
approaches for communication disorders caused by presumed laryngeal muscle dysfunction remain
theoretically speculative. Our long-term goal is to understand the laryngeal neuromuscular response to
increased voice use, such as vocal training and voice therapy, and decreased voice use, such as voice rest
and senescence. The overall objective of this proposal is to determine how the proteome and metabolome of
the thyroarytenoid muscle respond to vocalization training and aging. Our central hypothesis is that
vocalization training will increase signaling pathways for mitochondrial function and oxidative stress responses
and that aging will have unique proteomic and metabolomic effects in the thyroarytenoid muscle relative to the
limb muscles. This work will be accomplished through two aims. In male and female rats we will characterize
and identify specific biomarkers and biochemical pathways in the thyroarytenoid muscle indicative of
neuromuscular adaptations under the following two conditions: (1) vocalization training and (2) senescence
(aging). Specifically, we will broadly characterize muscle contractile properties, bioenergetics, and redox stress
responses within the proteins and metabolites of muscle tissue of the thyroarytenoid muscle. This work will
build on a previously established behavioral animal model involving training rats to increase their production of
ultrasonic vocalizations. Additionally, using the same proteomic and metabolomic approaches, we will
elucidate how age-related changes manifest across the lifespan by examining the thyroarytenoid muscle of
young adult, older adult, and senescent male and female rats, and comparing biomarkers in this muscle to
biomarkers in the gastrocnemius hindlimb. The study is innovative in its use of a behavioral animal model to
investigate the effects of laryngeal muscle use and senescence on neuromuscular mechanisms and in its
implementation of novel high-throughput proteomic and metabolomic approaches to examine laryngeal
neuromuscular structure and function. These multi-omics approaches will complement previous studies
conducted in our lab on neuromuscular junction and muscle fiber plasticity in normal and aging rodent models,
thereby laying the foundation for understanding the cellular and molecular neuromuscular pathways involved in
normal and aging intrinsic laryngeal muscle structure and function. This translational work will provide evidence
for future therapeutic targets for clinical populations such as presbyphonia and hyperfunctional voice disorders.
...

## Key facts

- **NIH application ID:** 9966242
- **Project number:** 1R21DC018107-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Aaron Matthew Johnson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,500
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966242

## Citation

> US National Institutes of Health, RePORTER application 9966242, Development of a behavioral rat model to assess proteomic and metabolomic adaptations of laryngeal muscles in response to vocal exercise (1R21DC018107-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9966242. Licensed CC0.

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