Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease.

Animals Axonal Transport Brain Chemistry Dopaminergic Neurons / metabolism Duodenum / innervation Humans Injections, Intramuscular Lewy Bodies / metabolism Maze Learning Memory Disorders / etiology Mice Mice, Inbred C57BL Mice, Knockout Models, Neurological Muscle, Smooth / innervation Nesting Behavior / physiology Parkinsonian Disorders / etiology Phosphorylation Protein Aggregates Protein Processing, Post-Translational Pylorus / innervation Rotarod Performance Test Vagotomy Vagus Nerve / metabolism alpha-Synuclein / administration & dosage
Braak hypothesis Lewy body pathology Parkinson’s disease gut to brain transmission motor symptoms neurodegeneration non-motor symptoms pre-formed fibrils vagus nerve α-synuclein

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
21 08 2019
Historique:
received: 24 07 2018
revised: 03 04 2019
accepted: 22 05 2019
pubmed: 1 7 2019
medline: 29 10 2019
entrez: 1 7 2019
Statut: ppublish

Résumé

Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer. Spread of pathologic α-syn in brain, as assessed by phosphorylation of serine 129 of α-syn, was observed first in the dorsal motor nucleus, then in caudal portions of the hindbrain, including the locus coeruleus, and much later in basolateral amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta. Moreover, loss of dopaminergic neurons and motor and non-motor symptoms were observed in a similar temporal manner. Truncal vagotomy and α-syn deficiency prevented the gut-to-brain spread of α-synucleinopathy and associated neurodegeneration and behavioral deficits. This study supports the Braak hypothesis in the etiology of idiopathic Parkinson's disease (PD).

Identifiants

DOI: 10.1016/j.neuron.2019.05.035 PMID: 31255487 PMC: PMC6706297
pubmed: 31255487
pii: S0896-6273(19)30488-X
doi: 10.1016/j.neuron.2019.05.035
pmc: PMC6706297
mid: NIHMS1530676
pii:
doi:

Substances chimiques

Protein Aggregates 0
Snca protein, mouse 0
alpha-Synuclein 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Video-Audio Media

Langues

eng

Sous-ensembles de citation

IM

Pagination

627-641.e7

Subventions

Organisme : NINDS NIH HHS
ID : P50 NS038377
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS082205
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS107404
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS098006
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Sangjune Kim (S)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Seung-Hwan Kwon (SH)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Tae-In Kam (TI)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Nikhil Panicker (N)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Senthilkumar S Karuppagounder (SS)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Saebom Lee (S)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Jun Hee Lee (JH)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Wonjoong Richard Kim (WR)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Minjee Kook (M)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Catherine A Foss (CA)

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Chentian Shen (C)

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Hojae Lee (H)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Subhash Kulkarni (S)

Center for Neurogastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Pankaj J Pasricha (PJ)

Center for Neurogastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Gabsang Lee (G)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Martin G Pomper (MG)

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Valina L Dawson (VL)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Ted M Dawson (TM)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: tdawson@jhmi.edu.

Han Seok Ko (HS)

Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA. Electronic address: hko3@jhmi.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Transport axonal › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Métabolisme › Chimie du cerveau › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Cellules › Neurones › Neurones dopaminergiques › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Système digestif › Tube digestif › Tube digestif supérieur › Duodénum › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Injections › Injections musculaires › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Cellules › Structures cellulaires › Corps d'inclusion › Corps de Lewy › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Apprentissage du labyrinthe › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Manifestations neurocomportementales › Troubles de la mémoire › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles neurologiques › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Tissus › Muscles › Muscles lisses › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement animal › Acte consommatoire › Comportement de nidification › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Troubles de la motricité › Syndromes parkinsoniens › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Métabolisme › Phosphorylation › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Structures macromoléculaires › Agrégats de protéines › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Système digestif › Tube digestif › Tube digestif supérieur › Estomac › Pylore › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Techniques d'investigation › Test du rotarod › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de neurochirurgie › Dénervation › Dénervation autonome › Parasympathectomie › Vagotomie › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Système nerveux › Système nerveux périphérique › Nerfs périphériques › Nerfs crâniens › Nerf vague › Transneuronal Propagation of Pathologic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › Transneuronal Propagation of Pathologic...