Beck Goichi, Hori Yumiko, Hayashi Yoshito, Morii Eiichi, Takehara Tetsuo, Mochizuki Hideki
Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Parkinsons Dis. 2020 Sep 23;2020:4687530. doi: 10.1155/2020/4687530. eCollection 2020.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor impairments, including constipation. Lewy bodies and neurites, the pathological hallmarks of PD, are found in the enteric nervous system (ENS) as well as the central nervous system. Constipation is a well-documented premotor symptom in PD, and recent reports have demonstrated Lewy pathology in gastrointestinal (GI) tissues of PD patients prior to the onset of motor symptoms.
In the present study, we assessed Lewy pathology in the GI tracts of seven PD patients who had undergone a gastrectomy, gastric polypectomy, or colonic polypectomy prior to the onset of motor symptoms in order to assess whether the presence of pathological Syn in the ENS could be a predictor for PD.
GI tissue samples were collected from control patients and patients with premotor PD. Immunohistochemistry was performed using primary antibodies against -synuclein (Syn) and phosphorylated Syn (pSyn), after which Lewy pathology in each sample was assessed.
In all control and premotor PD patients, accumulation of Syn was observed in the myenteric plexus in both the stomach and colon. In 82% (18/22) of control patients, mild-to-moderate accumulation of Syn was observed in the submucosal plexus. However, there was no deposition of pSyn in the ENS of control patients. In patients with premotor PD, abundant accumulation of Syn was observed in the myenteric plexus, similar to control patients. On the other hand, pSyn-positive aggregates were also observed in the nerve fibers in the muscularis propria in all examined patients with premotor PD (100%, 3/3), while the deposition of pSyn in the submucosal plexus was only observed in one patient (14%, 1/7).
Our results suggest that the detection of pSyn, but not Syn, especially in the muscularis propria of GI tracts, could be a sensitive prodromal biomarker for PD.
帕金森病（PD）是一种神经退行性疾病，其特征为运动和非运动功能障碍，包括便秘。路易小体和神经突是PD的病理标志，在肠神经系统（ENS）以及中枢神经系统中均有发现。便秘是PD中记录充分的运动前症状，最近的报告表明，在运动症状出现之前，PD患者的胃肠道（GI）组织中存在路易病理改变。
在本研究中，我们评估了7例在运动症状出现之前接受过胃切除术、胃息肉切除术或结肠息肉切除术的PD患者胃肠道中的路易病理改变，以评估ENS中病理性α-突触核蛋白（Syn）的存在是否可作为PD的预测指标。
从对照患者和运动前PD患者中收集GI组织样本。使用抗α-突触核蛋白（Syn）和磷酸化Syn（pSyn）的一抗进行免疫组织化学，然后评估每个样本中的路易病理改变。
在所有对照患者和运动前PD患者中，均在胃和结肠的肌间神经丛中观察到Syn的积聚。在82%（18/22）的对照患者中，在黏膜下神经丛中观察到轻度至中度的Syn积聚。然而，对照患者的ENS中未观察到pSyn的沉积。在运动前PD患者中，肌间神经丛中观察到与对照患者相似的大量Syn积聚。另一方面，在所有接受检查的运动前PD患者（100%，3/3）的固有肌层神经纤维中也观察到pSyn阳性聚集物，而仅在1例患者（14%，1/7）的黏膜下神经丛中观察到pSyn的沉积。
我们的结果表明，检测pSyn而非Syn，尤其是在胃肠道固有肌层中，可能是PD的一种敏感的前驱生物标志物。
