Duodenal alpha-Synuclein Pathology and Enteric Gliosis in Advanced Parkinson's Disease.

Humans Parkinson Disease / pathology alpha-Synuclein / metabolism Glial Fibrillary Acidic Protein / metabolism Gliosis Duodenum / chemistry
Parkinson's disease alpha-synuclein enteric nervous system gastrointestinal biopsies neuropathology

Journal

Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688

Informations de publication

Date de publication:
05 2023
Historique:
revised: 26 01 2023
received: 29 11 2022
accepted: 03 02 2023
medline: 13 6 2023
pubmed: 28 2 2023
entrez: 27 2 2023
Statut: ppublish

Résumé

The role of the gut-brain axis has been recently highlighted as a major contributor to Parkinson's disease (PD) physiopathology, with numerous studies investigating bidirectional transmission of pathological protein aggregates, such as α-synuclein (αSyn). However, the extent and the characteristics of pathology in the enteric nervous system have not been fully investigated. We characterized αSyn alterations and glial responses in duodenum biopsies of patients with PD by employing topography-specific sampling and conformation-specific αSyn antibodies. We examined 18 patients with advanced PD who underwent Duodopa percutaneous endoscopic gastrostomy and jejunal tube procedure, 4 untreated patients with early PD (disease duration <5 years), and 18 age- and -sex-matched healthy control subjects undergoing routine diagnostic endoscopy. A mean of four duodenal wall biopsies were sampled from each patient. Immunohistochemistry was performed for anti-aggregated αSyn (5G4) and glial fibrillary acidic protein antibodies. Morphometrical semiquantitative analysis was performed to characterize αSyn-5G4 Immunoreactivity for aggregated α-Syn was identified in all patients with PD (early and advanced) compared with controls. αSyn-5G4 We found evidence of synuclein pathology and gliosis in the duodenum of patients with PD, including early de novo cases. Future studies are required to evaluate how early in the disease process duodenal pathology occurs and its possible contribution to levodopa effect in chronic patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sections du résumé

BACKGROUND
The role of the gut-brain axis has been recently highlighted as a major contributor to Parkinson's disease (PD) physiopathology, with numerous studies investigating bidirectional transmission of pathological protein aggregates, such as α-synuclein (αSyn). However, the extent and the characteristics of pathology in the enteric nervous system have not been fully investigated.
OBJECTIVE
We characterized αSyn alterations and glial responses in duodenum biopsies of patients with PD by employing topography-specific sampling and conformation-specific αSyn antibodies.
METHODS
We examined 18 patients with advanced PD who underwent Duodopa percutaneous endoscopic gastrostomy and jejunal tube procedure, 4 untreated patients with early PD (disease duration <5 years), and 18 age- and -sex-matched healthy control subjects undergoing routine diagnostic endoscopy. A mean of four duodenal wall biopsies were sampled from each patient. Immunohistochemistry was performed for anti-aggregated αSyn (5G4) and glial fibrillary acidic protein antibodies. Morphometrical semiquantitative analysis was performed to characterize αSyn-5G4
RESULTS
Immunoreactivity for aggregated α-Syn was identified in all patients with PD (early and advanced) compared with controls. αSyn-5G4
CONCLUSIONS
We found evidence of synuclein pathology and gliosis in the duodenum of patients with PD, including early de novo cases. Future studies are required to evaluate how early in the disease process duodenal pathology occurs and its possible contribution to levodopa effect in chronic patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Identifiants

DOI: 10.1002/mds.29358 PMID: 36847308
pubmed: 36847308
doi: 10.1002/mds.29358
doi:

Substances chimiques

alpha-Synuclein 0
Glial Fibrillary Acidic Protein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

885-894

Informations de copyright

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Auteurs

Aron Emmi (A)

Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy.
Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases, Padua Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
ORCID: 0000-0002-2796-5676

Michele Sandre (M)

Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases, Padua Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.

Francesco Paolo Russo (FP)

Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.

Giulia Tombesi (G)

Department of Biology, University of Padova, Padova, Italy.

Federica Garrì (F)

Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases, Padua Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy.

Marta Campagnolo (M)

Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases, Padua Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
ORCID: 0000-0002-6394-7168

Miryam Carecchio (M)

Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases, Padua Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.

Roberta Biundo (R)

Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases, Padua Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
Department of General Psychology, University of Padova, Padova, Italy.

Gaya Spolverato (G)

Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.

Veronica Macchi (V)

Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.

Edoardo Savarino (E)

Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.

Fabio Farinati (F)

Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.

Piero Parchi (P)

Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada.
IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
ORCID: 0000-0002-9444-9524

Andrea Porzionato (A)

Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.

Luigi Bubacco (L)

Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.
Department of Biology, University of Padova, Padova, Italy.

Raffaele De Caro (R)

Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.

Gabor G Kovacs (GG)

Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.
Departments of Laboratory Medicine and Pathobiology and Medicine, University of Toronto, Toronto, Ontario, Canada.
Laboratory Medicine Program & Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.

Angelo Antonini (A)

Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases, Padua Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy.
Center for Neurodegenerative Disease Research (CESNE), Department of Neuroscience, University of Padova, Padova, Italy.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Duodenal alpha-Synuclein Pathology and Enteric...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Duodenal alpha-Synuclein Pathology and Enteric...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › Duodenal alpha-Synuclein Pathology and Enteric...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines de filaments intermédiaires › Protéine gliofibrillaire acide › Duodenal alpha-Synuclein Pathology and Enteric...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Gliose › Duodenal alpha-Synuclein Pathology and Enteric...
questionsmedicales.fr › Système digestif › Tube digestif › Tube digestif supérieur › Duodénum › Duodenal alpha-Synuclein Pathology and Enteric...