Exercise Effects on Early Vocal Ultrasonic Communication Dysfunction in a PINK1 Knockout Model of Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disease with vocal communication deficits that manifest early, progress, and are largely resistant to medical interventions; however, they do respond to exercise-based speech and voice therapies. OBJECTIVE AND METHODS: To study how exercise-based vocal treatment can affect the progression of communication deficits related to PD, we studied ultrasonic vocalizations (USVs) in rats with homozygous knockout (-/-) of PINK1, a gene mutation known to cause PD, under the manipulation of a behavioral vocal exercise paradigm that allows us to precisely control dose and timing of exercise in the prodromal (prior to diagnosis) stages.
RESULTS: We show that intensive vocal-training rescues frequency range and intensity deficits as well as leads to an increase in call complexity and duration of calls compared to sham-training; however, over time this training regime loses significant effect as the disease progresses. We also show effects of frequent handling and conspecific (male-female) interaction in the sham-training group as they demonstrated significantly higher call rate, intensity, frequency range, and call complexity compared to rats without any form of training and consequently less handling/interaction. Further, we confirm that this model exhibits progressive gross motor deficits that indicate neurodegeneration. DISCUSSION: This study suggests that the evolving nature of vocal communication deficits requires an adjustment of therapy targets and more intensive training over the course of this progressive disease and demonstrates the importance of frequent social experiences.