While people are often aware of the motor symptoms in Parkinson’s disease (PD), few know of the many non-motor symptoms, which patients report have a greater impact on their quality of life. Gastrointestinal (GI) dysfunction is one of the most common non-motor symptoms, which can occur at any stage of PD, even years prior to diagnosis, and can affect all sections along the GI tract causing a range of symptoms including drooling, gastroparesis and constipation. We have investigated whether a neurotoxin model of PD induced by rotenone, a mitochondrial complex I inhibitor, is capable of reproducing the GI dysfunction seen clinically. Sprague-Dawley rats were administered 2.75 mg/kg rotenone, 5 days/week for 4 weeks, via intraperitoneal injection. Rats underwent behavioural testing, including the one-hour stool and gastric emptying tests before GI contents and tissues were collected for microbiota and histological analysis. Rats exposed to rotenone had more days with evidence of diarrhoea and significantly delayed gastric emptying, reproducing the clinical symptom of gastroparesis. Microbiota analysis revealed alterations in the small intestine and colon of rotenone-treated rats, relatively consistent with changes described in PD patients. Histological analysis demonstrated mucosal thickening and goblet cell hyperplasia in the colon of rotenone rats, which may be an adaptive response to the toxin or changes in GI microbiota. Our results indicate that rotenone may be a good model for investigating the mechanisms involved with Parkinson’s GI symptoms and for screening potential therapeutic options as it is capable of recapitulating some key GI changes that occur during PD progression.

尽管人们通常都知道帕金森氏病（PD）的运动症状，但很少有人知道许多非运动症状，这些患者报告说，这会对他们的生活质量产生更大的影响。胃肠功能障碍是最常见的非运动症状之一，可发生在PD的任何阶段，甚至在诊断之前数年，并会影响GI道的所有部位，引起一系列症状，包括流口水，胃轻瘫和便秘。我们已经研究了鱼藤酮（线粒体复合体I抑制剂）诱导的PD的神经毒素模型是否能够重现临床上所见的GI功能障碍。Sprague-Dawley大鼠通过腹膜内注射，每周5天，每周4天服用2.75 mg / kg鱼藤酮。对老鼠进行行为测试，包括一小时的粪便和胃排空测试，然后收集胃肠道内容物和组织进行微生物群和组织学分析。暴露于鱼藤酮的大鼠有更多的腹泻天数，并显着延迟了胃排空，重现了胃轻瘫的临床症状。微生物群分析显示鱼藤酮治疗的大鼠小肠和结肠的改变，与PD患者中描述的改变相对一致。组织学分析表明鱼藤酮大鼠结肠粘膜增厚和杯状细胞增生，这可能是对毒素的适应性反应或胃肠道微生物群的变化。