Mu Liancai, Chen Jingming, Sobotka Stanislaw, Nyirenda Themba, Benson Brian, Gupta Fiona, Sanders Ira, Adler Charles H, Caviness John N, Shill Holly A, Sabbagh Marwan, Samanta Johan E, Sue Lucia I, Beach Thomas G
Upper Airway Research Laboratory, Department of Research, Hackensack University Medical Center, Hackensack, NJ, 07601, USA,
Dysphagia. 2015 Aug;30(4):404-17. doi: 10.1007/s00455-015-9612-7. Epub 2015 Jun 4.
Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.
吞咽困难在帕金森病（PD）中很常见，并会导致显著的发病率和死亡率。PD吞咽困难通常被解释为中枢运动控制功能障碍，这与该疾病的其他典型运动症状非常相似。然而，PD吞咽困难与运动症状的严重程度无关，对运动疗法也没有反应。已知PD患者咽部存在感觉缺陷，感觉受损可能导致吞咽困难。然而，PD患者咽部感觉缺陷的根本原因尚不清楚。我们推测，伴有感觉缺陷的PD吞咽困难可能是由于上消化道（UAT）感觉神经末梢的退化所致。我们之前已经表明，路易体型突触核蛋白病（LTS）存在于PD患者的主要咽部感觉神经中，而对照组中则没有。在本研究中，对UAT黏膜中的感觉末梢进行了研究，以确定LTS的存在和分布。从10名临床诊断和神经病理学确诊为PD的已故人类受试者（5名有吞咽困难，5名无吞咽困难）和4名年龄匹配的健康对照者中获取全层标本（舌-咽-喉-上食管）。从六个部位取样并进行磷酸化α-突触核蛋白（PAS）免疫染色。结果显示，所有PD受试者均存在PAS免疫反应性（PAS-ir）轴突，而对照组均未出现。值得注意的是，有吞咽困难的PD患者在启动吞咽反射的关键区域有更多的PAS-ir轴突。这些发现表明，路易体病理影响UAT特定区域的黏膜感觉轴突，可能与PD吞咽困难有关。
