Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation.
ABSTRACT Clinical studies suggest that gut disorders are common in Parkinson's disease, but the morphological basis is unknown. Depletion of dopamine-containing neurons in the central nervous system is a basic defect in Parkinson's disease. We compared colonic tissue from 11 patients with advanced Parkinson's disease, 17 with adenocarcinoma (normal tissue was studied), and five who underwent colectomy for severe constipation. Immunohistochemistry was used to stain myenteric and submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal polypeptide (VIP). Each class of neurons was quantified as a percentage of the total neuronal population stained for the marker protein gene product 9.5. Nine of the 11 Parkinson's disease patients had substantially fewer dopaminergic myenteric neurons than the other subjects (mean 0.4 [SE 0.2] vs 6.9 [2.3] in controls and 5.7 [2.0] in constipated subjects). There was very little difference between the groups in numbers of tyrosine-hydroxylase and VIP neurons. Two Parkinson's disease patients had similar distributions of all types of neurons, including dopaminergic myenteric neurons, to the controls. High-performance liquid chromatography showed lower levels of dopamine in the muscularis externa (but not mucosa) in four Parkinson's disease patients than in four controls (7.3 [5.1] vs 24.2 [4.6] nmol per g protein), but levels of dopamine metabolites were similar in the two groups. The identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinson's disease may lead to better treatment of colorectal dysfunction in this disease.
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ABSTRACT: Gastrointestinal (GI) symptoms are common among patients with Parkinson's disease (PD), due to both the disease itself and anti-PD drugs. We hypothesized that transdermal drug administration may result in fewer GI problems. This prospective observational study (ClinicalTrials.gov: NCT01159691) investigated effect of switching to rotigotine transdermal patch from oral anti-PD medications in patients with PD and existing GI symptoms. Patients were enrolled if their physician was planning to switch them to rotigotine because of GI symptoms experienced while receiving oral anti-PD medications. Effectiveness assessments included a visual analog scale (VAS) measuring intensity of GI symptoms from 0 (no disorder) to 100 mm (extremely severe disorder), a questionnaire on the frequency and intensity of six individual GI complaints (heartburn, bloating, nausea, vomiting, abdominal pain, diarrhea), each rated 0-12 for a sum score of 0-72, and patient satisfaction regarding GI symptoms over approximately 6 weeks after switching. Of 75 patients who received rotigotine, 58 had follow-up data available for final analysis. Intensity of GI complaints improved numerically on both the VAS (47.5 ± 24.4 mm [n = 65] at baseline, 19.7 ± 23.3 mm [n = 58] after around 6 weeks) and the sum score of GI complaints (11.2 ± 9.0 at baseline, 2.1 ± 4.4 [n = 58] after around 6 weeks). Fifty of 58 patients were "satisfied" or "very satisfied" regarding GI symptoms over around 6 weeks following switch to the patch. This study suggests that a switch from oral anti-PD medications to rotigotine transdermal patch may improve existing GI symptoms among patients with PD. Additional controlled studies are needed to confirm this finding. Copyright © 2014 Elsevier Ltd. All rights reserved.Parkinsonism & Related Disorders 12/2014; 21(3). DOI:10.1016/j.parkreldis.2014.11.024 · 4.13 Impact Factor
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ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system. Animal models have been invaluable tools for investigating the underlying mechanisms of the pathogenesis of PD and testing new potential symptomatic, neuroprotective and neurorestorative therapies. However, the usefulness of these models is dependent on how precisely they replicate the features of clinical PD with some studies now employing combined gene-environment models to replicate more of the affected pathways. The rotenone model of PD has become of great interest following the seminal paper by the Greenamyre group in 2000 (Betarbet et al., 2000). This paper reported for the first time that systemic rotenone was able to reproduce the two pathological hallmarks of PD as well as certain parkinsonian motor deficits. Since 2000, many research groups have actively used the rotenone model worldwide. This paper will review rotenone models, focusing upon their ability to reproduce the two pathological hallmarks of PD, motor deficits, extranigral pathology and non-motor symptoms. We will also summarize the recent advances in neuroprotective therapies, focusing on those that investigated non-motor symptoms and review rotenone models used in combination with PD genetic models to investigate gene-environment interactions.NeuroToxicology 12/2014; 46:101-116. DOI:10.1016/j.neuro.2014.12.002 · 3.05 Impact Factor
Journal of Parkinson's Disease 01/2014; 4(4):577-8. DOI:10.3233/JPD-149007 · 1.10 Impact Factor