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ID 53008
FullText URL
Author
Murakami, Shinki
Sogawa, Norio
Miyoshi, Ko
Abstract
Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice.
Keywords
Parkinson's disease
Rotenone
Enteric nervous system
Astrocytes
Metallothionein
Published Date
2014-10
Publication Title
Neurotoxicity Research
Volume
volume26
Issue
issue3
Publisher
Springer
Start Page
285
End Page
298
ISSN
1029-8428
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52964
language
英語
File Version
author
Refereed
True
DOI
Web of Science KeyUT