Department of Surgery, University of Wisconsin, Madison, Wisconsin, United States of America.
Department of Communication Sciences and Disorders, University of Wisconsin, Madison, Wisconsin, United States of America.
PLoS One. 2020 Oct 16;15(10):e0240366. doi: 10.1371/journal.pone.0240366. eCollection 2020.
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.
帕金森病（PD）与言语和吞咽困难有关，可能是由于广泛的大脑和神经系统区域的病理学所致。在 PD 的尸检研究中，已经报道了咽和喉神经和肌肉的病理学。然而，目前尚不清楚 PD 是否与舌部的神经肌肉变化有关。先前在 PD 的大鼠模型（Pink1-/-）中的研究表明，在临床前阶段存在口运动和吞咽缺陷，这表明这些功能存在感觉运动障碍。本研究假设 Pink1-/-大鼠在与野生型（WT）相比的舌内肌肉中表现出改变的舌功能，同时伴有神经肌肉差异。雄性 Pink1-/-和 WT 大鼠在 4 个月和 6 个月大时（每组 7-8 只大鼠）进行了行为性舌功能测定，这是疾病的早期时间点。在 6 个月时，对颏舌肌（GG）和茎突舌骨肌（SG）肌肉进行肌球蛋白重链同工型（MyHC）、α-突触核蛋白水平、肌纤维大小、中央核化肌纤维和神经肌肉接头（NMJ）神经支配的分析。与 WT 相比，Pink1-/-表现出更大的舌压力变异性，以及更大的舌压力和速度。此外，Pink1-/-在 SG 中显示出 MyHC 2a 的相对增加，但在 GG 中显示出典型的 MyHC 谱。Western blot 显示 GG 中的 Pink1-/-比 WT 具有更多的α-突触核蛋白，但在 SG 中则没有。在肌纤维大小、中央核化肌纤维或 NMJ 神经支配方面，Pink1-/-与 WT 之间没有差异。在两种基因型中都观察到α-突触核蛋白存在于神经、NMJ 和血管中。在这些早期疾病阶段的研究结果表明，在几个外围生物学指标上，存在微小变化或没有变化，并且舌肌的运动神经支配完好。未来的工作应该在疾病的后期阶段评估这些指标，以确定何时强大的病理外周变化会导致功能变化，以及中枢神经系统缺陷会导致行为变化。了解 PD 如何影响中枢和外周机制将有助于确定治疗言语和吞咽障碍的目标。
