Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza Università of Rome.
Department of Surgical Sciences, Sapienza University of Rome.
Eur J Histochem. 2021 Nov 2;65(4):3310. doi: 10.4081/ejh.2021.3310.
Alpha-synuclein (α-syn) is a presynaptic neuronal protein and its structural alterations play an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). It has been originally described in the brain and aggregated α-syn has also been found in the peripheral nerves including the enteric nervous system (ENS) of PD patients. ENS is a network of neurons and glia found in the gut wall which controls gastrointestinal function independently from the central nervous system. Moreover, two types of epithelial cells are crucial in the creation of an interface between the lumen and the ENS: they are the tuft cells and the enteroendocrine cells (EECs). In addition, the abundant enteric glial cells (EGCs) in the intestinal mucosa play a key role in controlling the intestinal epithelial barrier. Our aim was to localize and characterize the presence of α-syn in the normal human jejunal wall. Surgical specimens of proximal jejunum were collected from patients submitted to pancreaticoduodenectomy and intestinal sections underwent immunohistochemical procedure. Alpha-syn has been found both at the level of ENS and the epithelial cells. To characterize α-syn immunoreactive epithelial cells, we used markers such as choline acetyltransferase (ChAT), useful for the identification of tuft cells. Then we evaluated the co-presence of α-syn with serotonin (5-HT), expressed in EECs. Finally, we used the low-affinity nerve growth factor receptor (p75NTR), to detect peripheral EGCs. The presence of α-syn has been demonstrated in EECs, but not in the tuft cells. Additionally, p75NTR has been highlighted in EECs of the mucosal layer and co-localized with α-syn in EECs but not with ChAT-positive cells. These findings suggest that α-syn could play a possible role in synaptic transmission of the ENS and may contribute to maintain the integrity of the epithelial barrier of the small intestine through EECs.
α-突触核蛋白（α-syn）是一种突触前神经元蛋白，其结构改变在神经退行性疾病的发病机制中起着重要作用，如帕金森病（PD）。它最初在大脑中被描述，聚集的α-syn 也在包括 PD 患者的周围神经中被发现。肠神经系统（ENS）是存在于肠壁中的神经元和神经胶质细胞网络，它独立于中枢神经系统控制胃肠道功能。此外，两种类型的上皮细胞对于在腔和 ENS 之间创建界面至关重要：它们是微绒毛细胞和肠内分泌细胞（EEC）。此外，肠黏膜中丰富的肠胶质细胞（EGC）在控制肠道上皮屏障方面发挥着关键作用。我们的目的是定位和表征正常人类空肠壁中α-syn 的存在。从接受胰十二指肠切除术的患者中收集近端空肠的手术标本，并对肠段进行免疫组织化学处理。α-syn 存在于 ENS 和上皮细胞中。为了表征α-syn 免疫反应性上皮细胞，我们使用了一些标志物，如胆碱乙酰转移酶（ChAT），用于鉴定微绒毛细胞。然后，我们评估了α-syn 与 5-羟色胺（5-HT）的共存情况，5-HT 表达于 EEC 中。最后，我们使用低亲和力神经生长因子受体（p75NTR）来检测外周 EGC。已经证明 EEC 中存在α-syn，但微绒毛细胞中不存在。此外，黏膜层中的 EEC 中突出显示了 p75NTR，并与 EEC 中的α-syn 共定位，但与 ChAT 阳性细胞不共定位。这些发现表明，α-syn 可能在 ENS 的突触传递中发挥作用，并可能通过 EEC 来维持小肠上皮屏障的完整性。
