Modelling motor and non-motor signs of early-stage Parkinson's disease

Abstract

Introduction. As Parkinson's disease (PD) develops, a number of non-motor signs precede motor symptoms, including gastrointestinal tract dysfunction. Modelling early-stage PD to comprehensively assess the pattern of morphofunctional changes in the gastrointestinal tract is important in order to develop methods of early disease diagnosis and more effective treatment of autonomic disturbances that are typical in PD, and to increase the patients' quality of life. Study aim to offer a model of early-stage PD through long-term oral administration of small doses of the neurotoxin rotenone to rats, and to study the functional and immunohistochemical changes in the gastrointestinal tract of the experimental animals, as well as changes in the substantia nigra. Materials and methods. The experiment was conducted in male Wistar rats aged 3.03.5 months. The study group rats (n = 10) were given rotenone orally at a dose of 5 mg/kg, as a suspension in a 4% carboxymethyl cellulose solution, every second day for 7 months. The control group rats (n = 10) received only the 4% carboxymethyl cellulose solution. The animals' mobility was assessed at the start and end of the experiment using the open field and narrowing beam-walking test. Gastrointestinal motility was assessed by measuring the passage of dye from the pylorus in a caudal direction along the small intestine. The rats were decapitated and immunohistochemistry was used to assess the density of dopamine neurons in the substantia nigra, nerve fibres, and glia in the Auerbach's plexus of the small intestine, and the location of the total and phosphorylated alpha-synuclein in the enteric nervous system. Results. Rats in the study group had a statistically significant reduction in the number of dopamine neurons in the substantia nigra. Auerbach's plexus of the small intestine contained significantly less nerve fibres and glia, while fluorescence intensity for alpha-synuclein was increased. Phosphorylated alpha-synuclein was identified in the cholinergic and adrenergic fibres of Auerbach's plexus. Experimental animals had a statistically significant reduction in the gastric emptying rate and small intestine motility compared to the control group. Conclusion. The presented model of early-stage PD enables the physiological and immunohistochemical symptoms of gastrointestinal dysfunction, similar to that of patients with PD, to be replicated. They are based on intestinal denervation changes and accumulation of abnormal forms of alpha-synuclein in the enteric nervous system.