Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease

• Published in: Neuroscience letters 2009-12, Vol.467 (3), p.203-207
• Main Authors: Blandini, F., Balestra, B., Levandis, G., Cervio, M., Greco, R., Tassorelli, C., Colucci, M., Faniglione, M., Bazzini, E., Nappi, G., Clavenzani, P., Vigneri, S., De Giorgio, R., Tonini, M.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Colon - innervation; Colon - physiopathology; Constipation; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Enteric Nervous System - metabolism; Enteric Nervous System - pathology; Enteric Nervous System - physiopathology; Enteric neurons; Fundamental and applied biological sciences. Psychology; Gastrointestinal Diseases - etiology; Gastrointestinal Diseases - metabolism; Gastrointestinal Diseases - physiopathology; Gastrointestinal Motility - physiology; Gut dysfunction; Ileum - innervation; Ileum - physiopathology; Immunohistochemistry; Male; Medical sciences; Neurology; Neuronal Plasticity - physiology; Neuroplasticity; Nitrergic Neurons - metabolism; Nitrergic Neurons - pathology; Nitric oxide; Nitric Oxide - metabolism; Oxidopamine; Parkinson Disease - complications; Parkinsonian Disorders - complications; Rats; Rats, Sprague-Dawley; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.10.035

Patients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis.