A mouse model of adult-onset multiple system atrophy.

Animals Brain / metabolism Disease Models, Animal Mice Mice, Transgenic Motor Activity / physiology Multiple System Atrophy / genetics Oligodendroglia / metabolism Phosphorylation alpha-Synuclein / genetics
Cre-loxP technique Model mouse Multiple system atrophy Oligodendrocyte Phosphorylation α-Synuclein

Journal

Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169

Informations de publication

Date de publication:
07 2019
Historique:
received: 23 08 2018
revised: 20 03 2019
accepted: 21 03 2019
pubmed: 27 3 2019
medline: 10 1 2020
entrez: 27 3 2019
Statut: ppublish

Résumé

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder clinically characterized by autonomic failure in addition to various combinations of symptoms of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Despite extensive research, the mechanisms underlying the progression of MSA remain unknown. Animal models of human diseases that recapitulate their clinical, biochemical and pathological features are indispensable for increasing our understanding of their underlying molecular mechanisms, which allows preclinical studies to be advanced. Because the onset of MSA occurs in middle age, an animal model that first manifests abnormal protein aggregates in adulthood would be most appropriate. We therefore used the Cre-loxP system to express inducible α-synuclein (Syn), a major component of the pathological hallmark of MSA, to generate a mouse model of MSA. Beginning in adulthood, these MSA model mice express excessive levels of Syn in oligodendrocytes, resulting in abnormal Syn accumulation and modifications similar to those observed in human MSA pathology. Additionally, MSA model mice exhibit some clinical features of MSA, including decreased motor activity. These findings suggest that this new mouse model of MSA represents a useful tool for analyzing the pathophysiological alterations that underlie the progression of this disease.

Identifiants

DOI: 10.1016/j.nbd.2019.03.020 PMID: 30910745
pubmed: 30910745
pii: S0969-9961(18)30476-5
doi: 10.1016/j.nbd.2019.03.020
pii:
doi:

Substances chimiques

alpha-Synuclein 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

339-349

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Kunikazu Tanji (K)

Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan. Electronic address: kunikazu@hirosaki-u.ac.jp.

Yasuo Miki (Y)

Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.

Fumiaki Mori (F)

Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.

Yoshikazu Nikaido (Y)

Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.

Hidemi Narita (H)

Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; Department of Rehabilitation Sciences, School of Health Sciences, Hirosaki University of Health and Welfare, Hirosaki 036-8102, Japan.

Akiyoshi Kakita (A)

Department of Pathology, Brain Research Institute, University of Niigata, Niigata 951-8585, Japan.

Hitoshi Takahashi (H)

Department of Pathology, Brain Research Institute, University of Niigata, Niigata 951-8585, Japan.

Koichi Wakabayashi (K)

Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Mouvement › Activité motrice › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Atrophie multisystématisée › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Cellules › Névroglie › Oligodendroglie › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Métabolisme › Phosphorylation › A mouse model of adult-onset multiple system atrophy.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › A mouse model of adult-onset multiple system atrophy.