Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea.
Exp Neurobiol. 2011 Dec;20(4):181-8. doi: 10.5607/en.2011.20.4.181. Epub 2011 Dec 29.
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by abnormal deposition of α-synuclein aggregates in many regions of the central and peripheral nervous systems. Accumulating evidence suggests that the α-synuclein pathology initiates in a few discrete regions and spreads to larger areas in the nervous system. Recent pathological studies of PD patients have raised the possibility that the enteric nervous system is one of the initial sites of α-synuclein aggregation and propagation. Here, we evaluated the induction and propagation of α-synuclein aggregates in the enteric nervous system of the A53T α-synuclein transgenic mice after injection of human brain tissue extracts into the gastric walls of the mice. Western analysis of the brain extracts showed that the DLB extract contained detergent-stable α-synuclein aggregates, but the normal brain extract did not. Injection of the DLB extract resulted in an increased deposition of α-synuclein in the myenteric neurons, in which α-synuclein formed punctate aggregates over time up to 4 months. In these mice, inflammatory responses were increased transiently at early time points. None of these changes were observed in the A53T mice injected with saline or the normal brain extract, nor were these found in the wild type mice injected with the DLB extract. These results demonstrate that pathological α-synuclein aggregates present in the brain of DLB patient can induce the aggregation of endogenous α-synuclein in the myenteric neurons in A53T mice, suggesting the transmission of synucleinopathy lesions in the enteric nervous system.
帕金森病（PD）和路易体痴呆（DLB）的特征是在中枢和外周神经系统的许多区域异常沉积α-突触核蛋白聚集体。越来越多的证据表明，α-突触核蛋白病理学首先发生在少数离散区域，并在神经系统中传播到更大区域。最近对 PD 患者的病理学研究提出了这样一种可能性，即肠神经系统是α-突触核蛋白聚集和传播的初始部位之一。在这里，我们评估了在 A53T α-突触核蛋白转基因小鼠的胃壁注射人类脑组织提取物后，肠神经系统中α-突触核蛋白聚集体的诱导和传播。对脑提取物的 Western 分析表明，DLB 提取物含有去污剂稳定的α-突触核蛋白聚集体，但正常脑提取物没有。注射 DLB 提取物导致肠神经元中α-突触核蛋白沉积增加，随着时间的推移，α-突触核蛋白形成点状聚集体，最高可达 4 个月。在这些小鼠中，炎症反应在早期短暂增加。在注射生理盐水或正常脑提取物的 A53T 小鼠中未观察到这些变化，在注射 DLB 提取物的野生型小鼠中也未观察到这些变化。这些结果表明，DLB 患者脑内存在的病理性α-突触核蛋白聚集体可以诱导 A53T 小鼠肠神经元内内源性α-突触核蛋白的聚集，提示在肠神经系统中存在突触核蛋白病病变的传播。
