Rotenone induces gastrointestinal pathology and microbiota alterations in a rat model of Parkinson's disease.
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.
['Johnson|Michaela E|ME|', 'Stringer|Andrea|A|', 'Bobrovskaya|Larisa|L|']
D000818:Animals D003106:Colon D003967:Diarrhea D004195:Disease Models, Animal D005746:Gastric Emptying D005767:Gastrointestinal Diseases D008297:Male D064307:Microbiota D010302:Parkinson Disease, Secondary D051381:Rats D045442:Rotarod Performance Test D012402:Rotenone
Rotenone Gastrointestinal Microbiota Gastroparesis Diarrhea Parkinson’s disease