Session Information
Date: Wednesday, September 25, 2019
Session Title: Non-Motor Symptoms
Session Time: 1:15pm-2:45pm
Location: Agora 3 West, Level 3
Objective: To characterize the gastrointestinal (GI) phenotype in the 6-hydroxydopamine (6OHDA) rat model of Parkinson’s disease (PD).
Background: GI dysfunction, such as prolonged GI transit time and constipation, is a common non-motor symptom in PD patients. The mechanisms involved in PD-induced constipation remain unknown, although GI deficits may arise from lesions to the central nervous system (CNS) and/or enteric nervous system (ENS).
Method: Male Sprague Dawley rats were unilaterally injected with 6OHDA in the medial forebrain bundle. Amphetamine rotation testing was performed 2 weeks after lesioning to confirm the ablation of dopamine neurons in the pathway. Constipation and colon motility were assessed using the fecal pellet output test and bead expulsion test, respectively. Motor deficits were monitored using the beam traversal test. Lastly, colorectal propulsion was quantified through an in vivo experiment in anaesthetized rats. Colon pressureand the amount of fluid expelled were measured before and after the administration of a ghrelin receptor agonist (previously shown to stimulate nerve pathways that enhance colorectal propulsion).
Results: 6OHDA rats rotated significantly more when compared to sham animals (P<0.05), indicating damage to dopaminergic neurons. These rats also showed inhibited colonic propulsion, as assessed using the bead expulsion test. Administration of the ghrelin receptor agonist increased the number of contractions in both groups compared to baseline. There was no difference in the number of contractions between sham and 6OHDA rats. However, the amount of fluid expelled by 6OHDA rats was reduced in comparison to shams suggesting that 6OHDA animals have reduced colorectal propulsive activity. Interestingly, no significant change in fecal pellet output in response to a novel environment test or stool water content was observed. As expected, motor deficits were observed in 6OHDA rats 4 weeks post-surgery.
Conclusion: The 6OHDA rat model displays a GI phenotype with the presence of motor deficits 4 weeks post lesion. Although this model may not fully reproduce the human condition, it serves as a useful tool to understand the changes in the CNS and ENS associated with PD-induced GI dysfunction.
To cite this abstract in AMA style:
X. Chai, S. Diwakarla, R. Pustovit, R. Mcquade, M. Di Natale, C. Ermine, C. Parish, D. Finkelstein, J. Furness. Characterization of the gastrointestinal dysfunction in the 6-hydroxydopamine rat model of Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/characterization-of-the-gastrointestinal-dysfunction-in-the-6-hydroxydopamine-rat-model-of-parkinsons-disease/. Accessed December 9, 2024.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/characterization-of-the-gastrointestinal-dysfunction-in-the-6-hydroxydopamine-rat-model-of-parkinsons-disease/