INFLAMMATORY BOWEL DISEASE INDUCES α-SYNUCLEIN AGGREGATION IN GUT AND BRAIN
INFLAMMATORY BOWEL DISEASE INDUCES α-SYNUCLEIN AGGREGATION IN GUT AND BRAIN
ABSTRACT According to Braak’s hypothesis, it is plausible that Parkinsońs disease (PD) starts in the enteric nervous system (ENS) to spread the brain via the vagus nerve. Thus, we were wondering whether human inflammatory bowel diseases (IBD) can progress with appearance of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. Analysis of human gastrointestinal tract sections from IBD patients demonstrated the presence of pathogenic phosphorylated α-syn in both myenteric (Auerbach’s) and submucosal (Meissner’s) plexuses. Remarkably, PD subjects exhibit α-syn pathology in identical gastrointestinal locations. Analysis of human midbrain sections from IBD subjects revealed a clear displacement of neuromelanin in some nigral neurons from the ventral mesencephalon, which were inherently associated with presence of α-syn aggregates reminiscent of pale bodies. We also used different dextran sodium sulfate (DSS)-based rat models of gut inflammation (subchronic and chronic) to study the appearance of phosphorylated α-syn inclusions in both Auerbach’s and Meissner’s plexuses (gut), and in dopaminergic neuritic processes (brain) along with degeneration of nigral dopaminergic neurons, which are considered classical hallmarks of PD. Vagotomized DSS-treated animals exhibited pathological α-syn in the gut but failed to show dopaminergic cells degeneration and α-syn aggregation in the ventral mesencephalon. Taken together, these results strongly suggest that Braak’s hypothesis is plausible.
V¨￠zquez-Carretero Mar¨aa D.、Boza-Serrano Antonio、Garc¨aa-Revilla Juan、Deierborg Tomas、Rivas Eloy、Sibson Nicola R.、Labandeira-Garc¨aa Jos¨| L.、Machado Alberto、Herrera Antonio J.、Serres S¨|bastien、Economopoulus Vasiliki、Carvajal Ana E.、Oliva-Mart¨an Mar¨aa J.、de Pablos Roc¨ao M.、Soto Manuel Sarmiento、Espinosa-Oliva Ana M.、Santiago Marti、Venero Jos¨| L.、Peral Mar¨aa J.、Klementieva Oxana、Rodriguez-Perez Ana I.、Roca-Ceballos Mar¨aa A.、Garc¨aa-Miranda Pablo、Ruiz Roc¨ao
Departamento de Fisiolog¨aa, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de Sevilla||Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund UniversityInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund UniversityDepartamento de Anatom¨aa Patol¨?gica, Hospital Universitario Virgen del Roc¨aoCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of OxfordResearch Center for Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Health Research Institute (IDIS)||Networking Research Center on Neurodegenerative Diseases (CIBERNED)Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford||School of Life Sciences, University of NottinghamCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of OxfordDepartamento de Fisiolog¨aa, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de Sevilla||Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of OxfordInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaDepartamento de Fisiolog¨aa, Facultad de Farmacia, Universidad de SevillaExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund UniversityResearch Center for Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Health Research Institute (IDIS)||Networking Research Center on Neurodegenerative Diseases (CIBERNED)Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de SevillaDepartamento de Fisiolog¨aa, Facultad de Farmacia, Universidad de SevillaInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc¨ao/CSIC/Universidad de Sevilla, Sevilla, Spain and Departamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Farmacia, Universidad de Sevilla
神经病学、精神病学基础医学内科学
V¨￠zquez-Carretero Mar¨aa D.,Boza-Serrano Antonio,Garc¨aa-Revilla Juan,Deierborg Tomas,Rivas Eloy,Sibson Nicola R.,Labandeira-Garc¨aa Jos¨| L.,Machado Alberto,Herrera Antonio J.,Serres S¨|bastien,Economopoulus Vasiliki,Carvajal Ana E.,Oliva-Mart¨an Mar¨aa J.,de Pablos Roc¨ao M.,Soto Manuel Sarmiento,Espinosa-Oliva Ana M.,Santiago Marti,Venero Jos¨| L.,Peral Mar¨aa J.,Klementieva Oxana,Rodriguez-Perez Ana I.,Roca-Ceballos Mar¨aa A.,Garc¨aa-Miranda Pablo,Ruiz Roc¨ao.INFLAMMATORY BOWEL DISEASE INDUCES α-SYNUCLEIN AGGREGATION IN GUT AND BRAIN[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2022.01.26.477259.点此复制
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