Distinct pattern of enteric phospho-alpha-synuclein aggregates and gene expression profiles in patients with Parkinson's disease.
Distinct pattern of enteric phospho-alpha-synuclein aggregates and gene expression profiles in patients with Parkinson's disease.
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DOI：
10.1186/s40478-016-0408-2
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发表时间：
2017-01-05
影响因子：
7.1
通讯作者：
Wedel T
中科院分区：
文献类型：
--
作者：
Barrenschee M;Zorenkov D;Böttner M;Lange C;Cossais F;Scharf AB;Deuschl G;Schneider SA;Ellrichmann M;Fritscher-Ravens A;Wedel T
含有Lewy小体（LB）和Lewy神经突（LN）的磷酸化α-突触核蛋白（p-α-syn）是中枢神经系统（CNS）中帕金森病（PD）的神经病理学标志。由于它们也在PD患者的肠神经系统（ENS）中得到证实，因此本研究的目的是分析肠道p-α-syn阳性聚集体和肠道基因表达。从PD患者和对照组中获得直肠粘膜下活检组织，并对p-α-syn和PGP 9.5进行双标记免疫组织化学处理。对神经纤维和神经元胞体中的p-α-syn阳性聚集体进行形态计量学分析。采用qPCR研究α-syn和多巴胺能、多巴胺能、VIP（血管肠肽）能、胆碱能、毒蕈碱能神经递质系统的mRNA表达。PD组和对照组之间p-α-syn阳性神经纤维的频率相当。虽然两组中均检测到神经元p-α-syn阳性聚集体，但PD患者中p-α-syn阳性聚集体的总数和面积增加，小型和大型聚集体的数量也增加。PD患者多巴胺受体D1、VIP和5-羟色胺受体3A表达增加，而5-羟色胺受体4和毒蕈碱受体3（M3 R）表达下调。M3 R表达与小尺寸p-α-syn阳性聚集体的数量呈负相关。这些发现加强了这样的假设，即PD中p-α-syn增加的CNS病理学也适用于ENS，如果应用详细的形态测量学，并进一步了解PD中肠道基因表达的改变。尽管ENS中仅存在p-α-syn阳性聚集体不应被视为PD诊断的标准，但胃肠道活检中p-α-syn阳性聚集体的详细形态计量学分析可作为PD体内诊断的合适工具。本文的在线版本（doi：10.1186/s40478-016-0408-2）包含补充材料，可供授权用户使用。
Phosphorylated alpha-synuclein (p-α-syn) containing Lewy bodies (LBs) and Lewy neurites (LNs) are neuropathological hallmarks of Parkinson’s disease (PD) in the central nervous system (CNS). Since they have been also demonstrated in the enteric nervous system (ENS) of PD patients, the aim of the study was to analyze enteric p-α-syn positive aggregates and intestinal gene expression. Submucosal rectal biopsies were obtained from patients with PD and controls and processed for dual-label-immunohistochemistry for p-α-syn and PGP 9.5. p-α-syn positive aggregates in nerve fibers and neuronal somata were subjected to a morphometric analysis. mRNA expression of α-syn and dopaminergic, serotonergic, VIP (vaso intestinal peptide) ergic, cholinergic, muscarinergic neurotransmitter systems were investigated using qPCR. Frequency of p-α-syn positive nerve fibers was comparable between PD and controls. Although neuronal p-α-syn positive aggregates were detectable in both groups, total number and area of p-α-syn positive aggregates were increased in PD patients as was the number of small and large sized aggregates. Increased expression of dopamine receptor D1, VIP and serotonin receptor 3A was observed in PD patients, while serotonin receptor 4 and muscarinic receptor 3 (M3R) were downregulated. M3R expression correlated negative with the number of small sized p-α-syn positive aggregates. The findings strengthen the hypothesis that the CNS pathology of increased p-α-syn in PD also applies to the ENS, if elaborated morphometry is applied and give further insights in altered intestinal gene expression in PD. Although the mere presence of p-α-syn positive aggregates in the ENS should not be regarded as a criterion for PD diagnosis, elaborated morphometric analysis of p-α-syn positive aggregates in gastrointestinal biopsies could serve as a suitable tool for in-vivo diagnosis of PD. The online version of this article (doi:10.1186/s40478-016-0408-2) contains supplementary material, which is available to authorized users.
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影响因子：
2
作者：
Cersosimo MG
通讯作者：
Cersosimo MG
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
24.5
作者：
Costa, M.;Brookes, S. J. H.;Hennig, G. W.
通讯作者：
Hennig, G. W.
α-突触核蛋白在生理上是一种旋转的四聚体，可抵抗聚集。
影响因子：
64.8
作者：
Bartels, Tim;Choi, Joanna G.;Selkoe, Dennis J.
通讯作者：
Selkoe, Dennis J.
影响因子：
12.7
作者：
Gómez-Tortosa, E;Newell, K;Hyman, BT
通讯作者：
Hyman, BT