Institute of Bioengineering, Northeastern University, Shenyang, 110819, China.
Institute of Neuroscience, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Neurosci Bull. 2017 Oct;33(5):483-492. doi: 10.1007/s12264-017-0179-1. Epub 2017 Sep 18.
The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, α-syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α-Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.
肠神经系统（ENS）控制着胃肠道的功能，并与各种疾病有关，包括帕金森病（PD）。PD 是一种神经退行性疾病，其主要病理特征是路易体（LB）和路易神经突（LN）。除了 PD 的典型运动症状外，人们还注意到非运动症状，如便秘，这表明 ENS 功能障碍。在本研究中，我们在α-突触核蛋白（α-syn）转基因小鼠模型中描述了 ENS 中随年龄增长的形态改变和α-syn 的聚集，α-syn 是 LB 和 LN 的主要蛋白成分。我们发现，随着年龄的增长（从 1 周到 2 年），胃肠道 Meissner 丛和 Auerbach 丛神经元中的 α-syn 表达和积累逐渐增加。此外，α-syn 在丝氨酸 129 残基处的磷酸化程度逐渐增加，反映了该蛋白随时间的病理改变。此外，α-syn 存在于表达血管活性肠肽、神经元型一氧化氮合酶或钙视网膜蛋白的不同神经元亚型中。结果表明，BAC-α-Syn-GFP 转基因小鼠为研究 ENS 与 PD 发病机制之间的关系提供了一个独特的模型。
