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PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease

BACKGROUND: Positron Emission Tomography (PET) measurement was applied to the brain of the common marmoset, a small primate species, treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The marmoset shows prominent Parkinson’s disease (PD) signs due to dopaminergic neural degeneration....

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Autores principales: Ando, Kiyoshi, Obayashi, Shigeru, Nagai, Yuji, Oh-Nishi, Arata, Minamimoto, Takafumi, Higuchi, Makoto, Inoue, Takashi, Itoh, Toshio, Suhara, Tetsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466292/
https://www.ncbi.nlm.nih.gov/pubmed/23056291
http://dx.doi.org/10.1371/journal.pone.0046371
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author Ando, Kiyoshi
Obayashi, Shigeru
Nagai, Yuji
Oh-Nishi, Arata
Minamimoto, Takafumi
Higuchi, Makoto
Inoue, Takashi
Itoh, Toshio
Suhara, Tetsuya
author_facet Ando, Kiyoshi
Obayashi, Shigeru
Nagai, Yuji
Oh-Nishi, Arata
Minamimoto, Takafumi
Higuchi, Makoto
Inoue, Takashi
Itoh, Toshio
Suhara, Tetsuya
author_sort Ando, Kiyoshi
collection PubMed
description BACKGROUND: Positron Emission Tomography (PET) measurement was applied to the brain of the common marmoset, a small primate species, treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The marmoset shows prominent Parkinson’s disease (PD) signs due to dopaminergic neural degeneration. Recently, the transgenic marmoset (TG) carrying human PD genes is developing. For phenotypic evaluations of TG, non-invasive PET measurement is considered to be substantially significant. As a reference control for TG, the brain of the MPTP-marmoset as an established and valid model was scanned by PET. Behavioral analysis was also performed by recording locomotion of the MPTP-marmoset, as an objective measure of PD signs. METHODOLOGY/PRINCIPAL FINDINGS: Marmosets received several MPTP regimens (single MPTP regimen: 2 mg/kg, s.c., per day for 3 consecutive days) were used for PET measurement and behavioral observation. To measure immobility as a central PD sign, locomotion of marmosets in their individual living cages were recorded daily by infrared sensors. Daily locomotion counts decreased drastically after MPTP regimens and remained diminished for several months or more. PET scan of the brain, using [(11)C]PE2I as a ligand of the dopamine (DA) transporter, was performed once several months after the last MPTP regimen. The mean binding potential (BP(ND)) in the striatum (putamen and caudate) of the MPTP-marmoset group was significantly lower than that of the MPTP-free control group (n = 5 for each group). In the MPTP-marmosets, the decrease of BP(ND) in the striatum closely correlated with the decrease in locomotion counts (r = 0.98 in putamen and 0.91 in caudate). CONCLUSION/SIGNIFICANCE: The present characterization of neural degeneration using non-invasive PET imaging and of behavioral manifestation in the MPTP marmoset mimics typical PD characteristics and can be useful in evaluating the phenotype of TG marmosets being developed.
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spelling pubmed-34662922012-10-10 PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease Ando, Kiyoshi Obayashi, Shigeru Nagai, Yuji Oh-Nishi, Arata Minamimoto, Takafumi Higuchi, Makoto Inoue, Takashi Itoh, Toshio Suhara, Tetsuya PLoS One Research Article BACKGROUND: Positron Emission Tomography (PET) measurement was applied to the brain of the common marmoset, a small primate species, treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The marmoset shows prominent Parkinson’s disease (PD) signs due to dopaminergic neural degeneration. Recently, the transgenic marmoset (TG) carrying human PD genes is developing. For phenotypic evaluations of TG, non-invasive PET measurement is considered to be substantially significant. As a reference control for TG, the brain of the MPTP-marmoset as an established and valid model was scanned by PET. Behavioral analysis was also performed by recording locomotion of the MPTP-marmoset, as an objective measure of PD signs. METHODOLOGY/PRINCIPAL FINDINGS: Marmosets received several MPTP regimens (single MPTP regimen: 2 mg/kg, s.c., per day for 3 consecutive days) were used for PET measurement and behavioral observation. To measure immobility as a central PD sign, locomotion of marmosets in their individual living cages were recorded daily by infrared sensors. Daily locomotion counts decreased drastically after MPTP regimens and remained diminished for several months or more. PET scan of the brain, using [(11)C]PE2I as a ligand of the dopamine (DA) transporter, was performed once several months after the last MPTP regimen. The mean binding potential (BP(ND)) in the striatum (putamen and caudate) of the MPTP-marmoset group was significantly lower than that of the MPTP-free control group (n = 5 for each group). In the MPTP-marmosets, the decrease of BP(ND) in the striatum closely correlated with the decrease in locomotion counts (r = 0.98 in putamen and 0.91 in caudate). CONCLUSION/SIGNIFICANCE: The present characterization of neural degeneration using non-invasive PET imaging and of behavioral manifestation in the MPTP marmoset mimics typical PD characteristics and can be useful in evaluating the phenotype of TG marmosets being developed. Public Library of Science 2012-10-08 /pmc/articles/PMC3466292/ /pubmed/23056291 http://dx.doi.org/10.1371/journal.pone.0046371 Text en © 2012 Ando et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ando, Kiyoshi
Obayashi, Shigeru
Nagai, Yuji
Oh-Nishi, Arata
Minamimoto, Takafumi
Higuchi, Makoto
Inoue, Takashi
Itoh, Toshio
Suhara, Tetsuya
PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease
title PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease
title_full PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease
title_fullStr PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease
title_full_unstemmed PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease
title_short PET Analysis of Dopaminergic Neurodegeneration in Relation to Immobility in the MPTP-Treated Common Marmoset, a Model for Parkinson’s Disease
title_sort pet analysis of dopaminergic neurodegeneration in relation to immobility in the mptp-treated common marmoset, a model for parkinson’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466292/
https://www.ncbi.nlm.nih.gov/pubmed/23056291
http://dx.doi.org/10.1371/journal.pone.0046371
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