Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in Parkinson disease.
Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in Parkinson disease.
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DOI：
10.1097/nen.0b013e3182801cde
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发表时间：
2013-02
影响因子：
3.2
通讯作者：
Arizona Parkinson’s Disease Consortium
中科院分区：
文献类型：
--
作者：
Mu L;Sobotka S;Chen J;Su H;Sanders I;Adler CH;Shill HA;Caviness JN;Samanta JE;Beach TG;Arizona Parkinson’s Disease Consortium
帕金森病(PD)是一种以主要运动症状和中枢神经系统病理为主要特征的神经退行性疾病。由于目前的药物治疗通常可以稳定这些主要的运动症状，人们的注意力已经转移到帕金森病的其他运动和非运动症状上，这些症状对药物治疗具有抵抗力。帕金森病患者的吞咽困难可能是最重要的耐药症状，因为它会导致吸入和肺炎，这是导致死亡的主要原因。在这里，我们提出了帕金森病患者咽运动神经退行性变的直接证据。本研究对14例身体标本、10例帕金森病患者和4例年龄匹配的正常人的颈迷走神经、X神经咽支(Ph-X)和支配咽肌的咽丛进行了观察。用磷酸化α-突触核蛋白免疫组织化学方法检测咽神经突触核病。在所有帕金森病患者的X神经和Ph-X神经中发现了α-突触核蛋白聚集体，并在神经肌肉接头处发现了免疫反应阳性的肌内神经分支和轴突终末。提示咽部运动神经系统参与了帕金森病的病理过程。值得注意的是，与无吞咽困难的帕金森病患者相比，有吞咽困难的帕金森病患者咽神经中的α-突触核蛋白聚集体密度更高。帕金森病患者咽部运动受累可能是导致口咽吞咽困难的原因之一。
Parkinson’s disease (PD) is a neurodegenerative disease primarily characterized by cardinal motor symptoms and central nervous system pathology. As current drug therapies can often stabilize these cardinal motor symptoms attention has shifted to the other motor and non-motor symptoms of PD which are resistant to drug therapy. Dysphagia in PD is perhaps the most important drug resistant symptom as it leads to aspiration and pneumonia, the leading cause of death. Here, we present direct evidence for degeneration of the pharyngeal motor nerves in PD. In this study, we examined the cervical vagal (X) nerve, pharyngeal branch of the X nerve (Ph-X), and pharyngeal plexus innervating the pharyngeal muscles in 14 postmortem specimens, 10 subjects with PD and 4 age-matched control subjects. Synucleinopathy in the pharyngeal nerves was detected using an immunohistochemical method for phosphorylated α-synuclein. α-Synuclein aggregates were revealed in the X nerve and Ph-X and immunoreactive intramuscular nerve twigs and axon terminals within the neuromuscular junctions were identified in all the PD subjects and in none of the controls. These findings indicate that the motor nervous system of the pharynx is involved in the pathological process of PD. Notably, PD subjects with dysphagia had a higher density of α-synuclein aggregates in the pharyngeal nerves as compared with those without dysphagia. Motor involvement of the pharynx in PD appears to be one of the factors leading to oropharyngeal dysphagia commonly seen in PD patients.