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Miyazaki, Ikuko Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Isooka, Nami Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Imafuku, Fuminori Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sun, Jin Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kikuoka, Ryo Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Furukawa, Chieko Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Asanuma, Masato Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Abstract
Epidemiological studies demonstrated that pesticide exposure, such as rotenone and paraquat, increases the risk of Parkinson's disease (PD). Chronic systemic exposure to rotenone, a mitochondrial complex I inhibitor, could reproduce many features of PD. However, the adoption of the models is limiting because of variability in animal sensitivity and the inability of other investigators to consistently reproduce the PD neuropathology. In addition, most of rotenone models were produced in rats. Here, we tried to establish a high-reproducible rotenone model using C57BL/6J mice. The rotenone mouse model was produced by chronic systemic exposure to a low dose of rotenone (2.5 mg/kg/day) for 4 weeks by subcutaneous implantation of rotenone-filled osmotic mini pump. The rotenone-treated mice exhibited motor deficits assessed by open field, rotarod and cylinder test and gastrointestinal dysfunction. Rotenone treatment decreased the number of dopaminergic neuronal cells in the substantia nigra pars compacta (SNpc) and lesioned nerve terminal in the striatum. In addition, we observed significant reduction of cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) and the intestinal myenteric plexus. Moreover, alpha-synuclein was accumulated in neuronal soma in the SNpc, DMV and intestinal myenteric plexus in rotenone-treated mice. These data suggest that the low-dose rotenone mouse model could reproduce behavioral and central and peripheral neurodegenerative features of PD and be a useful model for investigation of PD pathogenesis.
Keywords
rotenone
Parkinson's disease
dopaminergic neuron
dorsal motor nucleus of the vagus
myenteric plexus
neurodegeneration
α-synuclein
motor deficit
Published Date
2020-05-04
Publication Title
International Journal of Molecular Sciences
Volume
volume21
Issue
issue9
Publisher
MDPI
Start Page
3254
ISSN
1422-0067
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2020 by the authors.
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isVersionOf https://doi.org/10.3390/ijms21093254
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http://creativecommons.org/licenses/by/4.0/