Alpha-Synuclein in Colonic Submucosa in Early Untreated Parkinson's Disease
Identifieur interne : 001215 ( Main/Exploration ); précédent : 001214; suivant : 001216Alpha-Synuclein in Colonic Submucosa in Early Untreated Parkinson's Disease
Auteurs : Kathleen M. Shannon [États-Unis] ; Ali Keshavarzian [États-Unis] ; Ece Mutlu [États-Unis] ; Hemraj B. Dodiya [États-Unis] ; Delia Daian [États-Unis] ; Jean A. Jaglin [États-Unis] ; Jeffrey H. Kordower [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2012.
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- Pascal (Inist)
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Abstract
The diagnosis of Parkinson's disease rests on motor signs of advanced central dopamine deficiency. There is an urgent need for disease biomarkers. Clinicopathological evidence suggests that α-synuclein aggregation, the pathological signature of Parkinson's disease, can be detected in gastrointestinal tract neurons in Parkinson's disease. We studied whether we could demonstrate α-synuclein pathology in specimens from unprepped flexible sigmoidoscopy of the distal sigmoid colon in early subjects with Parkinson's disease. We also looked for 3-nitrotyrosine, a marker of oxidative stress. Ten subjects with early Parkinson's disease not treated with dopaminergic agents (7 men; median age, 58.5 years; median disease duration, 1.5 years) underwent unprepped flexible sigmoidoscopy with biopsy of the distal sigmoid colon. Immunohistochemistry studies for αsynuclein and 3-nitrotyrosine were performed on biopsy specimens and control specimens from a tissue repository (23 healthy subjects and 23 subjects with inflammatory bowel disease). Nine of 10 Parkinson's disease samples were adequate for study. All showed staining for α-synuclein in nerve fibers in colonic submucosa. No control sample showed this pattern. A few showed light α-synuclein staining in round cells. 3-Nitrotyrosine staining was seen in 87% of Parkinson's disease cases but was not specific for Parkinson's disease. This study suggests a pattern of α-synuclein staining in Parkinson's disease that was distinct from healthy subjects and those with inflammatory bowel disease. The absence of this pattern in subjects with inflammatory bowel disease suggests it is not a sequel of inflammation or oxidative stress. 3-Nitrotyrosine immunostaining was common in all groups studied, suggesting oxidative stress in the coIonic submucosa.
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Shannon</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Departments of Neurological Sciences, Rush Medical College</s1><s2>Chicago, Illinois</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Keshavarzian, Ali" sort="Keshavarzian, Ali" uniqKey="Keshavarzian A" first="Ali" last="Keshavarzian">Ali Keshavarzian</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Gastroenterology and Nutrition, Rush Medical College</s1><s2>Chicago, Illinois</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Mutlu, Ece" sort="Mutlu, Ece" uniqKey="Mutlu E" first="Ece" last="Mutlu">Ece Mutlu</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Gastroenterology and Nutrition, Rush Medical College</s1><s2>Chicago, Illinois</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Dodiya, Hemraj B" sort="Dodiya, Hemraj B" uniqKey="Dodiya H" first="Hemraj B." last="Dodiya">Hemraj B. Dodiya</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Center for Brain Repair, Rush Medical College</s1><s2>Chicago, Illinois</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Daian, Delia" sort="Daian, Delia" uniqKey="Daian D" first="Delia" last="Daian">Delia Daian</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Gastroenterology and Nutrition, Rush Medical College</s1><s2>Chicago, Illinois</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Jaglin, Jean A" sort="Jaglin, Jean A" uniqKey="Jaglin J" first="Jean A." last="Jaglin">Jean A. Jaglin</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Departments of Neurological Sciences, Rush Medical College</s1><s2>Chicago, Illinois</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Kordower, Jeffrey H" sort="Kordower, Jeffrey H" uniqKey="Kordower J" first="Jeffrey H." last="Kordower">Jeffrey H. Kordower</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Center for Brain Repair, Rush Medical College</s1><s2>Chicago, Illinois</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biopsy</term><term>Colon</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Submucosa</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Côlon</term><term>Sousmuqueuse</term><term>Biopsie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The diagnosis of Parkinson's disease rests on motor signs of advanced central dopamine deficiency. There is an urgent need for disease biomarkers. Clinicopathological evidence suggests that α-synuclein aggregation, the pathological signature of Parkinson's disease, can be detected in gastrointestinal tract neurons in Parkinson's disease. We studied whether we could demonstrate α-synuclein pathology in specimens from unprepped flexible sigmoidoscopy of the distal sigmoid colon in early subjects with Parkinson's disease. We also looked for 3-nitrotyrosine, a marker of oxidative stress. Ten subjects with early Parkinson's disease not treated with dopaminergic agents (7 men; median age, 58.5 years; median disease duration, 1.5 years) underwent unprepped flexible sigmoidoscopy with biopsy of the distal sigmoid colon. Immunohistochemistry studies for αsynuclein and 3-nitrotyrosine were performed on biopsy specimens and control specimens from a tissue repository (23 healthy subjects and 23 subjects with inflammatory bowel disease). Nine of 10 Parkinson's disease samples were adequate for study. All showed staining for α-synuclein in nerve fibers in colonic submucosa. No control sample showed this pattern. A few showed light α-synuclein staining in round cells. 3-Nitrotyrosine staining was seen in 87% of Parkinson's disease cases but was not specific for Parkinson's disease. This study suggests a pattern of α-synuclein staining in Parkinson's disease that was distinct from healthy subjects and those with inflammatory bowel disease. The absence of this pattern in subjects with inflammatory bowel disease suggests it is not a sequel of inflammation or oxidative stress. 3-Nitrotyrosine immunostaining was common in all groups studied, suggesting oxidative stress in the coIonic submucosa.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Shannon, Kathleen M" sort="Shannon, Kathleen M" uniqKey="Shannon K" first="Kathleen M." last="Shannon">Kathleen M. Shannon</name></region><name sortKey="Daian, Delia" sort="Daian, Delia" uniqKey="Daian D" first="Delia" last="Daian">Delia Daian</name><name sortKey="Dodiya, Hemraj B" sort="Dodiya, Hemraj B" uniqKey="Dodiya H" first="Hemraj B." last="Dodiya">Hemraj B. Dodiya</name><name sortKey="Jaglin, Jean A" sort="Jaglin, Jean A" uniqKey="Jaglin J" first="Jean A." last="Jaglin">Jean A. Jaglin</name><name sortKey="Keshavarzian, Ali" sort="Keshavarzian, Ali" uniqKey="Keshavarzian A" first="Ali" last="Keshavarzian">Ali Keshavarzian</name><name sortKey="Kordower, Jeffrey H" sort="Kordower, Jeffrey H" uniqKey="Kordower J" first="Jeffrey H." last="Kordower">Jeffrey H. Kordower</name><name sortKey="Mutlu, Ece" sort="Mutlu, Ece" uniqKey="Mutlu E" first="Ece" last="Mutlu">Ece Mutlu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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