McQuade Rachel M, Singleton Lewis M, Wu Hongyi, Lee Sophie, Constable Remy, Di Natale Madeleine, Ringuet Mitchell T, Berger Joel P, Kauhausen Jessica, Parish Clare L, Finkelstein David I, Furness John B, Diwakarla Shanti
Department of Medicine, Western Health, Melbourne University, Sunshine, VIC, 3021, Australia.
College of Health and Biomedicine, Victoria University, Sunshine, VIC, 3021, Australia.
Sci Rep. 2021 Apr 12;11(1):7934. doi: 10.1038/s41598-021-86917-5.
Parkinson's disease (PD) is associated with neuronal damage in the brain and gut. This work compares changes in the enteric nervous system (ENS) of commonly used mouse models of PD that exhibit central neuropathy and a gut phenotype. Enteric neuropathy was assessed in five mouse models: peripheral injection of MPTP; intracerebral injection of 6-OHDA; oral rotenone; and mice transgenic for A53T variant human α-synuclein with and without rotenone. Changes in the ENS of the colon were quantified using pan-neuronal marker, Hu, and neuronal nitric oxide synthase (nNOS) and were correlated with GI function. MPTP had no effect on the number of Hu+ neurons but was associated with an increase in Hu+ nuclear translocation (P < 0.04). 6-OHDA lesioned mice had significantly fewer Hu+ neurons/ganglion (P < 0.02) and a reduced proportion of nNOS+ neurons in colon (P < 0.001). A53T mice had significantly fewer Hu+ neurons/area (P < 0.001) and exhibited larger soma size (P < 0.03). Treatment with rotenone reduced the number of Hu+ cells/mm in WT mice (P < 0.006) and increased the proportion of Hu+ translocated cells in both WT (P < 0.02) and A53T mice (P < 0.04). All PD models exhibited a degree of enteric neuropathy, the extent and type of damage to the ENS, however, was dependent on the model.
帕金森病（PD）与大脑和肠道中的神经元损伤有关。这项研究比较了常用的帕金森病小鼠模型中肠神经系统（ENS）的变化，这些模型表现出中枢神经病变和肠道表型。在五种小鼠模型中评估了肠神经病变：外周注射MPTP；脑内注射6-OHDA；口服鱼藤酮；以及携带和不携带鱼藤酮的A53T变体人α-突触核蛋白转基因小鼠。使用泛神经元标记物Hu和神经元型一氧化氮合酶（nNOS）对结肠ENS的变化进行量化，并与胃肠功能相关联。MPTP对Hu +神经元的数量没有影响，但与Hu +核转位增加有关（P <0.04）。6-OHDA损伤的小鼠每个神经节中Hu +神经元明显减少（P <0.02），结肠中nNOS +神经元的比例降低（P <0.001）。A53T小鼠每单位面积的Hu +神经元明显减少（P <0.001），且胞体尺寸更大（P <0.03）。鱼藤酮处理减少了野生型小鼠中每毫米Hu +细胞的数量（P <0.006），并增加了野生型（P <0.02）和A53T小鼠（P <0.04）中Hu +转位细胞的比例。所有帕金森病模型均表现出一定程度的肠神经病变，然而，ENS损伤的程度和类型取决于模型。
