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Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques

In neurodegenerative disorders, such as Parkinson's disease (PD), alpha-synuclein (α-syn) accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB). This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during...

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Autores principales: Kimura, Katsuo, Inoue, Ken-ichi, Kuroiwa, Yoshiyuki, Tanaka, Fumiaki, Takada, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115821/
https://www.ncbi.nlm.nih.gov/pubmed/27861638
http://dx.doi.org/10.1371/journal.pone.0166861
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author Kimura, Katsuo
Inoue, Ken-ichi
Kuroiwa, Yoshiyuki
Tanaka, Fumiaki
Takada, Masahiko
author_facet Kimura, Katsuo
Inoue, Ken-ichi
Kuroiwa, Yoshiyuki
Tanaka, Fumiaki
Takada, Masahiko
author_sort Kimura, Katsuo
collection PubMed
description In neurodegenerative disorders, such as Parkinson's disease (PD), alpha-synuclein (α-syn) accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB). This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.
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spelling pubmed-51158212016-12-08 Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques Kimura, Katsuo Inoue, Ken-ichi Kuroiwa, Yoshiyuki Tanaka, Fumiaki Takada, Masahiko PLoS One Research Article In neurodegenerative disorders, such as Parkinson's disease (PD), alpha-synuclein (α-syn) accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB). This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders. Public Library of Science 2016-11-18 /pmc/articles/PMC5115821/ /pubmed/27861638 http://dx.doi.org/10.1371/journal.pone.0166861 Text en © 2016 Kimura 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kimura, Katsuo
Inoue, Ken-ichi
Kuroiwa, Yoshiyuki
Tanaka, Fumiaki
Takada, Masahiko
Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques
title Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques
title_full Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques
title_fullStr Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques
title_full_unstemmed Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques
title_short Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques
title_sort propagated but topologically distributed forebrain neurons expressing alpha-synuclein in aged macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115821/
https://www.ncbi.nlm.nih.gov/pubmed/27861638
http://dx.doi.org/10.1371/journal.pone.0166861
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