| Autor: |
Ana M. Espinosa-Oliva, Rocío Ruiz, Manuel Sarmiento Soto, Antonio Boza-Serrano, Ana I. Rodriguez-Perez, María A. Roca-Ceballos, Juan García-Revilla, Marti Santiago, Sébastien Serres, Vasiliki Economopoulus, Ana E. Carvajal, María D. Vázquez-Carretero, Pablo García-Miranda, Oxana Klementieva, María J. Oliva-Martín, Tomas Deierborg, Eloy Rivas, Nicola R. Sibson, José L. Labandeira-García, Alberto Machado, María J. Peral, Antonio J. Herrera, José L. Venero, Rocío M. de Pablos |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.1101/2022.01.26.477259 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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