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: Epinephrine (E) and sympathetic nerve stimulation were described by Thomas Renton Elliott in 1905 for the first time. Dopamine (DA), norepinephrine (NE), E, and serotonin (5-HT) belong to the classic biogenic amines (or monoamines). Parkinson's disease (PD) is among the diseases in which it has been established that catecholamines may account for the neurodegeneration of central and peripheral catecholamine neural systems. PD is a chronic and progressive neurological disorder characterized by resting tremor, rigidity, and bradykinesia, affecting 2% of individuals above the age of 65 years. This disorder is a result of degeneration of DA-producing neurons of the substantia nigra and a significant loss of noradrenergic neurons in the locus coeruleus. In PD and other related neurodegerative diseases, catecholamines play the role of endogenous neurotoxins. Catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) catalyze the metabolism of monoamines. However, the monoamine transporters for DA, NE, and 5-HT namely DAT, NET, and SERT, respectively regulate the monoamine concentration. The metabolism of catecholamines and 5-HT involves common factors. Monoamine transporters represent targets for many pharmacological agents that affect brain function, including psychostimulators and antidepressants. In PD, polymorphisms of the COMT, MAO, DAT, NET, and 5- HTT genes may change the levels of biogenic amines and their metabolic products. The currently available therapies for PD improve the symptoms but do not halt the progression of the disease. The most effective treatment for PD patients is therapy with L-dopa. Combined therapy for PD involves a DA agonist and decarboxylase, MAOs and COMT inhibitors, and is the current optimal form of PD treatment maintaining monoamine balance.Current Genomics 12/2013; 14(8):518-33. DOI:10.2174/1389202914666131210210241 · 2.87 Impact Factor
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ABSTRACT: It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson's disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how this relates to protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson's disease.Free Radical Biology and Medicine 05/2013; 62. DOI:10.1016/j.freeradbiomed.2013.05.001 · 5.71 Impact Factor
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ABSTRACT: Background. Loss of normal bowel function caused by nerve injury, neurological disease or congenital defects of the nervous system is termed neurogenic bowel dysfunction (NBD). It usually includes combinations of fecal incontinence, constipation, abdominal pain and bloating. When standard treatment of NBD fails surgical procedures are often needed. Neurostimulation has also been investigated, but no consensus exists about efficacy or clinical use. Methods. A systematic literature search of NBD treated by sacral anterior root stimulation (SARS), sacral nerve stimulation (SNS), peripheral nerve stimulation, magnetic stimulation, and nerve re-routing was made in Pubmed, Embase, Scopus, and the Cochrane Library. Results. SARS improves bowel function in some patients with complete spinal cord injury (SCI). Nerve re-routing is claimed to facilitate defecation through mechanical stimulation of dermatomes in patients with complete or incomplete SCI or myelomeningocele. SNS can reduce NBD in selected patients with a variety of incomplete neurological lesions. Peripheral stimulation using electrical stimulation or magnetic stimulation may represent non-invasive alternatives. Conclusion. Numerous methods of neurostimulation to treat NBD have been investigated in pilot studies or retrospective studies. Therefore, larger controlled trials with well-defined inclusion criteria and endpoints are recommended before widespread clinical use of neurostimulation against NBD.Gastroenterology Research and Practice 03/2013; 2013:563294. DOI:10.1155/2013/563294 · 1.50 Impact Factor