Objective: The goal of this study was to examine the effect of a potential underlying mechanism responsible for the complex voice deficits that exist in Parkinson’s Diseases (PD), aggregation of the protein alpha-synuclein.

Background: Voice deficits are common in PD and significantly impact quality of life. However, despite their impact, there are currently no treatments that target the underlying pathophysiology of PD in the cranial sensorimotor system.

Method: An alpha-synuclein transgenic mouse model with a fibril seeding approach was used in this study. This model leads to more rapid development of pathology and allows for the study of the propagation of abnormal alpha-synuclein over long distances throughout the cranial sensorimotor system in an efficient and disease-relevant manner. Sixteen transgenic mice and 13 wild-type control mice have initially been analyzed in this preliminary study. Mice of each genotype were assigned to either fibrillar (experimental) or monomeric alpha-synuclein (control) injection into the striatum. Baseline and post-injection acoustic measurements of rodent ultrasonic vocalizations were acquired.

Results: No genotype difference was found at baseline, indicating that overexpression of the human A53T mutation alone does not result in a change in vocal communication in this mouse model.  Following injection, at the 2-month post-injection time point, all animals called significantly less than at baseline regardless of their genetic background or type of injection [F(1,25) = 187.8, p = 0.0001]. Analyses of objective vocalization characteristics, later timepoints, and additional mice with injections into the laryngeal musculature is ongoing.

Conclusion: Results depict the development of a mouse model that allows for manipulation of alpha-synuclein within discrete areas of the cranial sensorimotor system and enables the analysis of relevant vocalization behaviors. Results provide a critical foundational understanding of the role of aggregated alpha-synuclein in voice deficits in PD. Future work will continue to refine the mouse model to develop disease-modifying treatments to reduce or eliminate the burden of PD-specific voice disorders.

A previous version of this abstract, including preliminary data that has been updated, was presented as a poster at the World Parkinson’s Congress (WPC) July 6^th, 2023.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-aggregate-pathology-in-the-cranial-sensorimotor-system-in-a-mouse-model-of-parkinsons-disease/