TY - JOUR
T1 - Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation
AU - Singaram, C.
AU - Gaumnitz, E. A.
AU - Torbey, C.
AU - Ashraf, W.
AU - Quigley, E. M.M.
AU - Sengupta, A.
AU - Pfeiffer, R.
N1 - Funding Information:
We thank-Mr Mark A Sweet and Ms Margaret A Casper (University of Wisconsin) for technical support; Prof V Singaram for help with references, and the Parkinson Society for providing tissues for the study. This study was supported by grants from Graduate and Medical School of the University of Wisconsin, Madison VA GRECC, VA MERIT, American Foundation for Aging Research, and US-Israel Binational
PY - 1995/9/30
Y1 - 1995/9/30
N2 - Summary. 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.
AB - Summary. 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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U2 - 10.1016/S0140-6736(95)92707-7
DO - 10.1016/S0140-6736(95)92707-7
M3 - Article
C2 - 7564669
AN - SCOPUS:0029097763
SN - 0140-6736
VL - 346
SP - 861
EP - 864
JO - The Lancet
JF - The Lancet
IS - 8979
ER -