Abstract
Parkinson disease (PD) is associated with speech and swallowing difficulties likely due to pathology in widespread brain and nervous system regions. In post-mortem studies of PD, pathology has been reported in pharyngeal and laryngeal nerves and muscles. However, it is unknown whether PD is associated with neuromuscular changes in the tongue. Prior work in a rat model of PD (Pink1-/-) showed oromotor and swallowing deficits in the premanifest stage which suggested sensorimotor impairments of these functions. The present study tested the hypothesis that Pink1-/- rats show altered tongue function coinciding with neuromuscular differences within tongue muscles compared to wildtype (WT). Male Pink1-/- and WT rats underwent behavioral tongue function assays at 4 and 6 months of age (n = 7-8 rats per group), which are time points early in the disease. At 6 months, genioglossus (GG) and styloglossus (SG) muscles were analyzed for myosin heavy chain isoforms (MyHC), α-synuclein levels, myofiber size, centrally nucleated myofibers, and neuromuscular junction (NMJ) innervation. Pink1-/- showed greater tongue press force variability, and greater tongue press forces and rates as compared to WT. Additionally, Pink1-/- showed relative increases of MyHC 2a in SG, but typical MyHC profiles in GG. Western blots revealed Pink1-/- had more α-synuclein protein than WT in GG, but not in SG. There were no differences between Pink1-/- and WT in myofiber size, centrally-nucleated myofibers, or NMJ innervation. α-synuclein protein was observed in nerves, NMJ, and vessels in both genotypes. Findings at these early disease stages suggest small changes or no changes in several peripheral biological measures, and intact motor innervation of tongue muscles. Future work should evaluate these measures at later disease stages to determine when robust pathological peripheral change contributes to functional change, and what CNS deficits cause behavioral changes. Understanding how PD affects central and peripheral mechanisms will help determine therapy targets for speech and swallowing disorders.
Highlights
Parkinson disease (PD) involves widespread pathology in central and peripheral substrates [1, 2]
Prior studies have reported that dysphagia in late stages of PD coincides with pathological myofiber type grouping, evidence of myofiber degeneration, and pathology in neuromuscular junction (NMJ) [15, 17, 36, 37]
The majority of muscle biology assays did not corroborate conclusions of robust biological distinctions between these muscles in the degree to which they were influenced by genotype
Summary
Parkinson disease (PD) involves widespread pathology in central and peripheral substrates [1, 2]. PD is classically defined by central dopamine loss, our understanding of the widespread dysfunction that causes motor, sensory, autonomic, sleep, mood, speech, and cognitive issues is evolving [3, 4]. Difficulty swallowing, occurs in a high percentage of patients with PD [5]. Dysphagia can emerge early in PD, even in the premanifest (preclinical) stage, prior to the appearance of classic motor signs. Swallowing involves highly coordinated movements of the tongue muscles, and functional studies of the oropharyngeal swallow in patients with PD have reported alterations of tongue movements during swallow, including altered tongue strength and altered timing of movements [7]. Dysphagia does not reliably respond to standard PD treatments including levodopa or deep brain stimulation [5, 6, 8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
