BACKGROUND AND AIM Patients with Parkinson's disease (PD) are often characterized by functional gastrointestinal disorders. Such disturbances can occur at all stages of PD and precede the typical motor symptoms of the disease by many years. However, the morphological alterations associated with intestinal disturbances in PD are undetermined. This study examined the remodelling of colonic wall in 6-hydroxydopamine (6-OHDA)-induced PD rats. METHODS 8 weeks after 6-OHDA injection animals were sacrificed. Inflammatory infiltrates, collagen deposition and remodelling of intestinal epithelial barrier and tunica muscularis in the colonic wall were assessed by histochemistry, immunohistochemistry, immunofluorescence and western blot analysis. RESULTS 6-OHDA rats displayed significant alterations of colonic tissues as compared with controls. Signs of mild inflammation (eosinophil infiltration) and a transmural deposition of collagen fibres were observed. Superficial colonic layers were characterized by severe morphological alterations. In particular, lining epithelial cells displayed a reduced claudin-1 and transmembrane 16A/Anoctamin 1 (TMEM16A/ANO1) expression; goblet cells increased their mucin expression; colonic crypts were characterized by an increase in proliferating epithelial cells; the density of S100-positive glial cells and vimentin-positive fibroblast-like cells was increased as well. Several changes were found in the tunica muscularis: downregulation of α-smooth muscle actin/desmin expression and increased proliferation of smooth muscle cells; increased vimentin expression and proliferative phenotype in myenteric ganglia; reduction of interstitial cells of Cajal (ICCs) density. CONCLUSIONS A pathological remodelling occurs in the colon of 6-OHDA rats. The main changes include: enhanced fibrotic deposition; alterations of the epithelial barrier; activation of mucosal defense; reduction of ICCs. These results indicate that central nigrostriatal denervation is associated with histological changes in the large bowel at mucosal, submucosal and muscular level. These alterations might represent morphological correlates of digestive symptoms in PD.

中文翻译：

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多巴胺能黑质纹状体神经变性后结肠壁的病理重塑。

背景和目的帕金森氏病（PD）患者通常以功能性胃肠道疾病为特征。此类疾病可在PD的所有阶段发生，并在疾病的典型运动症状发作数年之前出现。但是，与PD肠道紊乱相关的形态学改变尚未确定。这项研究检查了6-羟基多巴胺（6-OHDA）诱导的PD大鼠结肠壁的重塑。方法注射6-OHDA后8周处死动物。通过组织化学，免疫组织化学，免疫荧光和蛋白质印迹分析评估了结肠壁的炎症浸润，胶原蛋白沉积以及肠上皮屏障和肌膜的重塑。结果6-OHDA大鼠与对照组相比显示出结肠组织的显着改变。观察到轻度炎症（嗜酸性粒细胞浸润）和胶原纤维透壁沉积的迹象。浅表结肠层的特征是严重的形态学改变。特别是，衬里的上皮细胞显示出减少的claudin-1和跨膜16A / Anoctamin 1（TMEM16A / ANO1）表达。杯状细胞增加了黏蛋白的表达；结肠隐窝的特征在于增殖的上皮细胞增加；S100阳性胶质细胞和波形蛋白阳性成纤维细胞样细胞的密度也增加。在肌膜中发现了一些变化：α-平滑肌肌动蛋白/结蛋白表达的下调和平滑肌细胞增殖的增加；肌膜神经节中波形蛋白的表达增加和增殖表型；减少间质细胞的Cajal（ICC）密度。结论6-OHDA大鼠结肠发生病理重塑。主要变化包括：纤维化沉积增强；上皮屏障的改变；激活粘膜防御；减少ICC。这些结果表明中央黑纹状体去神经与粘膜，粘膜下层和肌肉水平的大肠组织学改变有关。这些改变可能代表PD中消化系统症状的形态学相关性。这些结果表明中央黑纹状体去神经支配与大肠粘膜，粘膜下和肌肉水平的组织学变化有关。这些改变可能代表PD中消化系统症状的形态学相关性。这些结果表明中央黑纹状体去神经与粘膜，粘膜下层和肌肉水平的大肠组织学改变有关。这些改变可能代表PD中消化系统症状的形态学相关性。