Neuroprotective effects of metallothionein against rotenone-induced myenteric neurodegeneration in parkinsonian mice

Shinki Murakami, Ikuko Miyazaki, Norio Sogawa, Ko Miyoshi, Masato Asanuma

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)285-298
Number of pages14
JournalNeurotoxicity Research
Volume26
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

Rotenone
Metallothionein
Neuroprotective Agents
Neurology
Enteric Nervous System
Knockout Mice
Neurons
Parkinson Disease
Myenteric Plexus
Dopaminergic Neurons
Inbred C57BL Mouse
Astrocytes
Central Nervous System
Chemical activation
Neurodegenerative diseases
Oxidative stress
Pathology
Recombinant Proteins
Neurodegenerative Diseases
Oxidative Stress

Keywords

  • Astrocytes
  • Enteric nervous system
  • Metallothionein
  • Parkinson's disease
  • Rotenone

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology
  • Medicine(all)

Cite this

Neuroprotective effects of metallothionein against rotenone-induced myenteric neurodegeneration in parkinsonian mice. / Murakami, Shinki; Miyazaki, Ikuko; Sogawa, Norio; Miyoshi, Ko; Asanuma, Masato.

In: Neurotoxicity Research, Vol. 26, No. 3, 2014, p. 285-298.

Research output: Contribution to journalArticle

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