Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria.
Cell Biology and Neurotoxicity Unit, Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, Ekiti State, Nigeria.
Psychopharmacology (Berl). 2020 Nov;237(11):3225-3236. doi: 10.1007/s00213-020-05605-w. Epub 2020 Jul 10.
The asymptomatic and clinical stages of Parkinson's disease (PD) are associated with comorbid non-motor symptoms including gastrointestinal (GI) dysfunction. Although the neuroprotective and gastroprotective roles of kolaviron (KV) have been reported independently, whether KV-mediated GI-protective capacity could be beneficial in PD is unknown. We therefore investigated the modulatory effects of KV on the loss of dopaminergic neurons, locomotor abnormalities, and ileal oxidative damage when rats are lesioned in the nigrostriatal pathway. KV treatment markedly suppressed the behavioral deficit and apomorphine-induced rotations associated with rotenone lesioning. KV attenuated the loss of nigrostriatal dopaminergic neurons and perturbations in the striatal glucose-regulated protein (GRP78) and X-box binding protein 1 (XBP1) levels. Ileal epithelial injury following stereotaxic rotenone infusion was associated with oxidative stress and marked inhibition of acetylcholine esterase activity and reduced expression of occludin in the crypt and villi. While KV treatment attenuated the redox imbalance in the gut and enhanced occludin immunoreactivity, acetylcholinesterase activity was not affected. Our data demonstrate ileal oxidative damage as a characteristic non-motor gut dysfunction in PD while showing the potential dual efficacy of KV in the attenuation of both neural defects and gut abnormalities associated with PD.
帕金森病（PD）的无症状和临床阶段与胃肠道（GI）功能障碍等非运动症状有关。尽管 kolaviron（KV）的神经保护和胃保护作用已被独立报道，但 KV 介导的 GI 保护能力是否对 PD 有益尚不清楚。因此，我们研究了 KV 对黑质纹状体通路损伤大鼠多巴胺能神经元丢失、运动异常和回肠氧化损伤的调节作用。KV 治疗显著抑制了与鱼藤酮损伤相关的行为缺陷和阿扑吗啡诱导的旋转。KV 减轻了黑质纹状体多巴胺能神经元的丢失以及纹状体葡萄糖调节蛋白（GRP78）和 X 盒结合蛋白 1（XBP1）水平的紊乱。立体定向鱼藤酮输注后回肠上皮损伤与氧化应激以及乙酰胆碱酯酶活性的显著抑制和隐窝和绒毛中闭合蛋白表达减少有关。虽然 KV 治疗减轻了肠道的氧化失衡并增强了闭合蛋白免疫反应性，但乙酰胆碱酯酶活性没有受到影响。我们的数据表明，回肠氧化损伤是 PD 中一种特征性的非运动性肠道功能障碍，同时显示 KV 在减轻与 PD 相关的神经缺陷和肠道异常方面的双重功效。
