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Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model

According to a few studies, α-synuclein (αSyn) propagation has been suggested to play a key role in the pathomechanism of Parkinson's disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are not well understood with regard to temporal relationshi...

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Autores principales: Lai, Thuy Thi, Kim, Yun Joong, Nguyen, Phuong Thi, Koh, Young Ho, Nguyen, Tinh Thi, Ma, Hyeo-il, Kim, Young Eun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523784/
https://www.ncbi.nlm.nih.gov/pubmed/34675786
http://dx.doi.org/10.3389/fnint.2021.715190
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author Lai, Thuy Thi
Kim, Yun Joong
Nguyen, Phuong Thi
Koh, Young Ho
Nguyen, Tinh Thi
Ma, Hyeo-il
Kim, Young Eun
author_facet Lai, Thuy Thi
Kim, Yun Joong
Nguyen, Phuong Thi
Koh, Young Ho
Nguyen, Tinh Thi
Ma, Hyeo-il
Kim, Young Eun
author_sort Lai, Thuy Thi
collection PubMed
description According to a few studies, α-synuclein (αSyn) propagation has been suggested to play a key role in the pathomechanism of Parkinson's disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are not well understood with regard to temporal relationship. In this study, with the help of the PD mouse model injected with intrastriatal αSyn preformed fibril (PFF), the temporal evolution of αSyn propagation, inflammation, and neurodegeneration was explored in the perspective of the striatum and the whole brain. In the PFF-injected striatum, inflammatory response cells, including microglia and astrocytes, were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. Afterward, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavioral phenotype. Similar patterns of forefront eruption of inflammation and then followed by αSyn propagation were noted in the opposite striatum, which were not injured by PFF injection. In analyzing the whole brain, inflammatory responses were activated at the earliest stage, and the soluble αSyn expression increased concurrently. The inflammatory response decreased afterward, and the accumulation of the insoluble form of αSyn increased behind it. Our results suggested that the inflammatory response may precede the accumulation of the pathologic form of αSyn; thereafter, the neurodegeneration and motor dysfunction followed αSyn proliferation in the PD mouse model. From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing the PD animal model and monitoring the effect of interventional therapy.
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spelling pubmed-85237842021-10-20 Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model Lai, Thuy Thi Kim, Yun Joong Nguyen, Phuong Thi Koh, Young Ho Nguyen, Tinh Thi Ma, Hyeo-il Kim, Young Eun Front Integr Neurosci Neuroscience According to a few studies, α-synuclein (αSyn) propagation has been suggested to play a key role in the pathomechanism of Parkinson's disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are not well understood with regard to temporal relationship. In this study, with the help of the PD mouse model injected with intrastriatal αSyn preformed fibril (PFF), the temporal evolution of αSyn propagation, inflammation, and neurodegeneration was explored in the perspective of the striatum and the whole brain. In the PFF-injected striatum, inflammatory response cells, including microglia and astrocytes, were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. Afterward, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavioral phenotype. Similar patterns of forefront eruption of inflammation and then followed by αSyn propagation were noted in the opposite striatum, which were not injured by PFF injection. In analyzing the whole brain, inflammatory responses were activated at the earliest stage, and the soluble αSyn expression increased concurrently. The inflammatory response decreased afterward, and the accumulation of the insoluble form of αSyn increased behind it. Our results suggested that the inflammatory response may precede the accumulation of the pathologic form of αSyn; thereafter, the neurodegeneration and motor dysfunction followed αSyn proliferation in the PD mouse model. From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing the PD animal model and monitoring the effect of interventional therapy. Frontiers Media S.A. 2021-10-05 /pmc/articles/PMC8523784/ /pubmed/34675786 http://dx.doi.org/10.3389/fnint.2021.715190 Text en Copyright © 2021 Lai, Kim, Nguyen, Koh, Nguyen, Ma and Kim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Lai, Thuy Thi
Kim, Yun Joong
Nguyen, Phuong Thi
Koh, Young Ho
Nguyen, Tinh Thi
Ma, Hyeo-il
Kim, Young Eun
Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model
title Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model
title_full Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model
title_fullStr Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model
title_full_unstemmed Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model
title_short Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model
title_sort temporal evolution of inflammation and neurodegeneration with alpha-synuclein propagation in parkinson's disease mouse model
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523784/
https://www.ncbi.nlm.nih.gov/pubmed/34675786
http://dx.doi.org/10.3389/fnint.2021.715190
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