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首页> 外文期刊>Neurobiology of disease >Expression pattern and localization of alpha-synuclein in the human enteric nervous system
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Expression pattern and localization of alpha-synuclein in the human enteric nervous system

机译：α-突触核蛋白在人肠神经系统中的表达模式和定位

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Background: Alpha-synuclein (α-syn) is abundantly expressed in the central nervous system and involved in the regulation of neurotransmission. Insoluble fibrils of phosphorylated α-synuclein (p-α-syn) have been implicated in several neurodegenerative diseases (e.g. Parkinson's disease, Alzheimer's disease). The aim of the study was to determine the gene expression pattern and localization of α-syn/p-α-syn in the human enteric nervous system (ENS). Methods: Human colonic specimens (n = 13, 15-83. years) were processed for α-syn and p-α-syn immunohistochemistry. Colocalization of α-syn was assessed by dual-labeling with pan-neuronal markers (PGP 9.5, HuC/D). For qPCR studies, tissue was obtained from full-thickness sections, tunica muscularis, submucosa, mucosa, and laser-microdissected (LMD) enteric ganglia. Results: Highest α-syn levels were detectable within the tunica muscularis and submucosa. Ganglia isolated by LMD showed high expression of α-syn mRNA. All myenteric and submucosal ganglia and nerve fibers were immunoreactive for α-syn. Dual-labeling revealed colocalization of α-syn with both pan-neuronal markers. p-α-syn immunoreactivity was consistently observed in specimens from adults with increasing age. Conclusions: α-syn is abundantly expressed in all nerve plexus of the human ENS including both neuronal somata and processes. The presence of p-α-syn within the ENS is a regular finding in adults with increasing age and may not be regarded as pathological correlate. The data provide a basis to unravel the functions of α-syn and to evaluate altered α-syn in enteric neuropathies and α-synucleinopathies of the CNS with gastrointestinal manifestations.
机译：背景：α-突触核蛋白（α-syn）在中枢神经系统中大量表达，并参与神经传递的调节。磷酸化的α-突触核蛋白（p-α-syn）的不溶性原纤维与几种神经退行性疾病（例如帕金森氏病，阿尔茨海默氏病）有关。这项研究的目的是确定人类肠道神经系统（ENS）中α-syn/p-α-syn的基因表达模式和定位。方法：对人类结肠标本（n = 13、15-83。岁）进行α-syn和p-α-syn免疫组织化学处理。 α-syn的共定位通过泛神经元标记（PGP 9.5，HuC / D）的双重标记进行评估。对于qPCR研究，从全层切片，肌膜，粘膜下层，粘膜和激光显微切割（LMD）肠神经节中获取组织。结果：在肌膜和粘膜下层可检测到最高的α-syn水平。 LMD分离的神经节显示高表达的α-synmRNA。所有的肠系膜和粘膜下神经节和神经纤维对α-syn具有免疫反应性。双重标记揭示了α-syn与两个泛神经标记物共定位。随着年龄的增长，在成人标本中始终观察到p-α-syn免疫反应性。结论：α-syn在人类ENS的所有神经丛中都大量表达，包括神经元的躯体和过程。 ENS中p-α-syn的存在是成年人年龄增长的常规发现，可能不被视为病理相关因素。该数据为阐明α-syn的功能以及评估肠胃病表现的中枢神经系统的肠神经病和α-突触核蛋白病的改变提供了基础。

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