Functional characterization of extrinsic tongue muscles in the Pink1-/- rat model of Parkinson disease.
Functional characterization of extrinsic tongue muscles in the Pink1-/- rat model of Parkinson disease.
复制标题
DOI：
10.1371/journal.pone.0240366
复制
发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Ciucci MR
中科院分区：
文献类型：
--
作者：
Glass TJ;Kelm-Nelson CA;Szot JC;Lake JM;Connor NP;Ciucci MR
帕金森病（PD）与语言和吞咽困难有关，这可能是由于广泛的大脑和神经系统区域的病理所致。在PD的尸检研究中，已报告咽和喉神经和肌肉的病理学。然而，目前尚不清楚PD是否与舌头的神经肌肉变化有关。先前在PD大鼠模型（Pink 1-/-）中的研究显示，在表现前阶段存在吞咽和吞咽缺陷，这表明这些功能存在感觉运动障碍。本研究验证了Pink 1-/-大鼠与野生型（WT）相比，舌肌内神经肌肉差异与舌功能改变一致的假设。雄性Pink 1-/-和WT大鼠在4月龄和6月龄（每组n = 7-8只大鼠）时进行行为舌功能测定，这是疾病早期的时间点。在6个月时，分析颏舌肌（GG）和茎突舌肌（SG）肌肉的肌球蛋白重链亚型（MyHC）、α-突触核蛋白水平、肌纤维大小、中央有核肌纤维和神经肌肉接头（NMJ）神经支配。与WT相比，Pink 1-/-显示出更大的舌压力变化性，以及更大的舌压力和速率。此外，Pink 1-/-在SG中显示了MyHC 2a的相对增加，但在GG中显示了典型的MyHC谱。Western印迹显示Pink 1-/-在GG中比WT有更多的α-synuclein蛋白，但在SG中没有。Pink 1-/-和WT在肌纤维大小、中央核肌纤维或NMJ神经支配方面没有差异。在两种基因型的神经、NMJ和血管中观察到α-突触核蛋白蛋白。这些早期疾病阶段的发现表明，几种外周生物学指标变化很小或没有变化，舌肌运动神经支配完好。未来的工作应该在疾病后期评估这些措施，以确定何时出现强烈的病理性外周变化导致功能变化，以及哪些CNS缺陷导致行为变化。了解PD如何影响中枢和外周机制将有助于确定言语和吞咽障碍的治疗目标。
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.
登录
查看更多内容
影响因子：
2.5
作者：
Kelm-Nelson CA;Stevenson SA;Ciucci MR
通讯作者：
Ciucci MR
影响因子：
5.2
作者：
Jones, Corinne A.;Ciucci, Michelle R.
通讯作者：
Ciucci, Michelle R.
影响因子：
2.4
作者：
Adreani, C. M.;Li, Z. B.;Parente, E. J.
通讯作者：
Parente, E. J.
影响因子：
4
作者：
Hegland, Karen W.;Troche, Michelle;Brandimore, Alexandra
通讯作者：
Brandimore, Alexandra
影响因子：
1.9
作者：
Fuh, JL;Lee, RC;Liu, HC
通讯作者：
Liu, HC