Colonic biopsies to assess the neuropathology of Parkinson's disease and its relationship with symptoms.
Colonic biopsies to assess the neuropathology of Parkinson's disease and its relationship with symptoms.
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DOI：
10.1371/journal.pone.0012728
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发表时间：
2010-09-14
期刊：
影响因子：
3.7
通讯作者：
Derkinderen P
中科院分区：
文献类型：
--
作者：
Lebouvier T;Neunlist M;Bruley des Varannes S;Coron E;Drouard A;N'Guyen JM;Chaumette T;Tasselli M;Paillusson S;Flamand M;Galmiche JP;Damier P;Derkinderen P
帕金森病（PD）患者的肠神经系统（ENS）中存在路易体和路易神经突（LN）。本研究的目的是使用常规结肠镜活检（1）深入分析整个结肠粘膜下神经丛（SMP）的肠道病理学，（2）将病理负荷与神经和胃肠道（GI）症状相关联。共纳入10例对照和29例PD患者，根据疾病持续时间分为3组。分别使用统一帕金森病评定量表第三部分和罗马III问卷评估PD和GI症状。在全结肠镜检查过程中，从升结肠和降结肠采集了4份活检标本。使用抗磷酸化α-突触核蛋白、神经丝NF 220 kDa（NF）和酪氨酸羟化酶（TH）的抗体进行免疫组织化学分析。LN的密度，标记的抗磷酸化的α-突触核蛋白抗体，使用定量评分进行评价。Lewy病理学在21例患者的结肠活检中明显，而对照组中无一例。与对照组相比，在PD患者的SMP中观察到每个神经节的NF免疫反应神经元数量减少。ENS中LN的量与神经元计数呈负相关，与左旋多巴无反应特征和便秘呈正相关。通过常规结肠镜活检对ENS进行分析是用于PD的死前神经病理学诊断的有用工具，并且还提供了对运动和非运动症状进展的洞察。
The presence of Lewy bodies and Lewy neurites (LN) has been demonstrated in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. The aims of the present research were to use routine colonoscopy biopsies (1) to analyze, in depth, enteric pathology throughout the colonic submucosal plexus (SMP), and (2) to correlate the pathological burden with neurological and gastrointestinal (GI) symptoms. A total of 10 control and 29 PD patients divided into 3 groups according to disease duration were included. PD and GI symptoms were assessed using the Unified Parkinson's Disease Rating Scale part III and the Rome III questionnaire, respectively. Four biopsies were taken from the ascending and descending colon during the course of a total colonoscopy. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein, neurofilaments NF 220 kDa (NF) and tyrosine hydroxylase (TH). The density of LN, labeled by anti-phosphorylated alpha-synuclein antibodies, was evaluated using a quantitative rating score. Lewy pathology was apparent in the colonic biopsies from 21 patients and in none of the controls. A decreased number of NF-immunoreactive neurons per ganglion was observed in the SMP of PD patients compared to controls. The amount of LN in the ENS was inversely correlated with neuronal count and positively correlated with levodopa-unresponsive features and constipation. Analysis of the ENS by routine colonoscopy biopsies is a useful tool for pre-mortem neuropathological diagnosis of PD, and also provides insight into the progression of motor and non-motor symptoms.
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