Structural alterations of the intestinal epithelial barrier in Parkinson’s disease
Identifieur interne : 000503 ( Main/Curation ); précédent : 000502; suivant : 000504Structural alterations of the intestinal epithelial barrier in Parkinson’s disease
Auteurs : Thomas Clairembault [France] ; Laurène Leclair-Visonneau [France] ; Emmanuel Coron [France] ; Arnaud Bourreille [France] ; Séverine Le Dily [France] ; Fabienne Vavasseur [France] ; Marie-Françoise Heymann [France] ; Michel Neunlist [France] ; Pascal Derkinderen [France]Source :
- Acta Neuropathologica Communications [ 2051-5960 ] ; 2015.
Abstract
Functional and morphological alterations of the intestinal epithelial barrier (IEB) have been consistently reported in digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. There is mounting evidence that Parkinson’s disease (PD) is not only a brain disease but also a digestive disorder. Gastrointestinal involvement is a frequent and early event in the course of PD, and it may be critically involved in the early development of the disease. We therefore undertook the present survey to investigate whether changes in the IEB function and/or morphology occur in PD. Colonic biopsies were performed in 31 PD patients and 11 age-matched healthy controls. The para- and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux respectively, in colonic biopsies mounted in Ussing chambers. The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively. The para- and transcellular permeability were not different between PD patients and controls. The expression of occludin, but not ZO-1, was significantly lower in colonic samples from PD patients as compared to controls and the cellular distribution of both proteins was altered in colonic mucosal specimens from PD patients. Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.
The online version of this article (doi:10.1186/s40478-015-0196-0) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s40478-015-0196-0
PubMed: 25775153
PubMed Central: 4353469
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<wicri:regionArea>CHU Nantes, Institut des Maladies de l’Appareil Digestif, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff4">Inserm, CIC-04, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Inserm, CIC-04, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Heymann, Marie Francoise" sort="Heymann, Marie Francoise" uniqKey="Heymann M" first="Marie-Françoise" last="Heymann">Marie-Françoise Heymann</name>
<affiliation wicri:level="3"><nlm:aff id="Aff2">University Nantes, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>University Nantes, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff5">CHU Nantes, Service d’Anatomie Pathologique, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>CHU Nantes, Service d’Anatomie Pathologique, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff6">Inserm, UMR957, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Inserm, UMR957, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Neunlist, Michel" sort="Neunlist, Michel" uniqKey="Neunlist M" first="Michel" last="Neunlist">Michel Neunlist</name>
<affiliation wicri:level="3"><nlm:aff id="Aff1">Inserm U913, 1 rue Gaston Veil, Nantes, F-44035 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Inserm U913, 1 rue Gaston Veil, Nantes, F-44035 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff2">University Nantes, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>University Nantes, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff3">CHU Nantes, Institut des Maladies de l’Appareil Digestif, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>CHU Nantes, Institut des Maladies de l’Appareil Digestif, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Derkinderen, Pascal" sort="Derkinderen, Pascal" uniqKey="Derkinderen P" first="Pascal" last="Derkinderen">Pascal Derkinderen</name>
<affiliation wicri:level="3"><nlm:aff id="Aff1">Inserm U913, 1 rue Gaston Veil, Nantes, F-44035 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Inserm U913, 1 rue Gaston Veil, Nantes, F-44035 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff2">University Nantes, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>University Nantes, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff4">Inserm, CIC-04, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Inserm, CIC-04, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff7">CHU Nantes, Department of Neurology, Nantes, F-44093 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>CHU Nantes, Department of Neurology, Nantes, F-44093 France</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">France</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Acta Neuropathologica Communications</title>
<idno type="eISSN">2051-5960</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>Functional and morphological alterations of the intestinal epithelial barrier (IEB) have been consistently reported in digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. There is mounting evidence that Parkinson’s disease (PD) is not only a brain disease but also a digestive disorder. Gastrointestinal involvement is a frequent and early event in the course of PD, and it may be critically involved in the early development of the disease. We therefore undertook the present survey to investigate whether changes in the IEB function and/or morphology occur in PD. Colonic biopsies were performed in 31 PD patients and 11 age-matched healthy controls. The para- and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux respectively, in colonic biopsies mounted in Ussing chambers. The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively. The para- and transcellular permeability were not different between PD patients and controls. The expression of occludin, but not ZO-1, was significantly lower in colonic samples from PD patients as compared to controls and the cellular distribution of both proteins was altered in colonic mucosal specimens from PD patients. Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.</p>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s40478-015-0196-0) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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</author>
<author><name sortKey="Graham, Wv" uniqKey="Graham W">WV Graham</name>
</author>
<author><name sortKey="Turner, Jr" uniqKey="Turner J">JR Turner</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name>
</author>
</analytic>
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</author>
<author><name sortKey="De Vos, Ra" uniqKey="De Vos R">RA de Vos</name>
</author>
<author><name sortKey="Bohl, J" uniqKey="Bohl J">J Bohl</name>
</author>
<author><name sortKey="Del Tredici, K" uniqKey="Del Tredici K">K Del Tredici</name>
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</analytic>
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<biblStruct><analytic><author><name sortKey="Hollander, D" uniqKey="Hollander D">D Hollander</name>
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<biblStruct><analytic><author><name sortKey="Davies, Kn" uniqKey="Davies K">KN Davies</name>
</author>
<author><name sortKey="King, D" uniqKey="King D">D King</name>
</author>
<author><name sortKey="Billington, D" uniqKey="Billington D">D Billington</name>
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<author><name sortKey="Barrett, Ja" uniqKey="Barrett J">JA Barrett</name>
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</analytic>
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<biblStruct><analytic><author><name sortKey="Hughes, Aj" uniqKey="Hughes A">AJ Hughes</name>
</author>
<author><name sortKey="Daniel, Se" uniqKey="Daniel S">SE Daniel</name>
</author>
<author><name sortKey="Lees, Aj" uniqKey="Lees A">AJ Lees</name>
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<biblStruct><analytic><author><name sortKey="Cameron, Hl" uniqKey="Cameron H">HL Cameron</name>
</author>
<author><name sortKey="Perdue, Mh" uniqKey="Perdue M">MH Perdue</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Lai, S W" uniqKey="Lai S">S-W Lai</name>
</author>
<author><name sortKey="Liao, K F" uniqKey="Liao K">K-F Liao</name>
</author>
<author><name sortKey="Lin, C L" uniqKey="Lin C">C-L Lin</name>
</author>
<author><name sortKey="Sung, F C" uniqKey="Sung F">F-C Sung</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Coss Adame, E" uniqKey="Coss Adame E">E Coss-Adame</name>
</author>
<author><name sortKey="Rao, Ssc" uniqKey="Rao S">SSC Rao</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Braak, H" uniqKey="Braak H">H Braak</name>
</author>
<author><name sortKey="Rub, U" uniqKey="Rub U">U Rub</name>
</author>
<author><name sortKey="Gai, Wp" uniqKey="Gai W">WP Gai</name>
</author>
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</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Hopkins, Da" uniqKey="Hopkins D">DA Hopkins</name>
</author>
<author><name sortKey="Bieger, D" uniqKey="Bieger D">D Bieger</name>
</author>
<author><name sortKey="Devente, J" uniqKey="Devente J">J deVente</name>
</author>
<author><name sortKey="Steinbusch, Wm" uniqKey="Steinbusch W">WM Steinbusch</name>
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