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Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease

BACKGROUND: It remains unclear why patients with young-onset Parkinson’s disease more often develop levo-dihydroxyphenylalanine (L-dopa)-induced dyskinesia (LID) and have a more severe form than patients with old-onset Parkinson’s disease. Previous studies using animal models have failed to show you...

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Autores principales: Nishijima, Haruo, Kimura, Tamaki, Mori, Fumiaki, Wakabayashi, Koichi, Kinoshita, Iku, Nakamura, Takashi, Kon, Tomoya, Suzuki, Chieko, Tomiyama, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155371/
https://www.ncbi.nlm.nih.gov/pubmed/34054505
http://dx.doi.org/10.3389/fnagi.2021.650350
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author Nishijima, Haruo
Kimura, Tamaki
Mori, Fumiaki
Wakabayashi, Koichi
Kinoshita, Iku
Nakamura, Takashi
Kon, Tomoya
Suzuki, Chieko
Tomiyama, Masahiko
author_facet Nishijima, Haruo
Kimura, Tamaki
Mori, Fumiaki
Wakabayashi, Koichi
Kinoshita, Iku
Nakamura, Takashi
Kon, Tomoya
Suzuki, Chieko
Tomiyama, Masahiko
author_sort Nishijima, Haruo
collection PubMed
description BACKGROUND: It remains unclear why patients with young-onset Parkinson’s disease more often develop levo-dihydroxyphenylalanine (L-dopa)-induced dyskinesia (LID) and have a more severe form than patients with old-onset Parkinson’s disease. Previous studies using animal models have failed to show young-onset Parkinson’s disease enhances LID. OBJECTIVES: To evaluate the association of age at dopaminergic denervation (onset age) and initiation of L-dopa treatment (treatment age) with LID development in model rats. METHODS: We established rat models of young- and old-lesioned Parkinson’s disease (6-hydroxydopamine lesions at 10 and 88 weeks of age, respectively). Dopaminergic denervation was confirmed by the rotational behavior test using apomorphine. Rats in the young-lesioned group were allocated to either L-dopa treatment at a young or old age, or saline treatment. Rats in the old-lesioned group were allocated to either L-dopa treatment or saline group. We evaluated L-dopa-induced abnormal involuntary movements during the 14-day treatment period. We also examined preprodynorphin mRNA expression in the striatum (a neurochemical hallmark of LID) and the volume of the medial globus pallidus (a pathological hallmark of LID). RESULTS: LID-like behavior was enhanced in L-dopa-treated young-lesioned rats compared with L-dopa-treated old-lesioned rats. Preprodynorphin mRNA expression was higher in L-dopa-treated young-lesioned rats than in in L-dopa-treated old-lesioned rats. The volume of the medial globus pallidus was greater in L-dopa-treated young-lesioned rats than in L-dopa-treated old-lesioned rats. Treatment age did not affect LID-like behavior or the degree of medial globus pallidus hypertrophy in the young-lesioned model. CONCLUSION: Both dopaminergic denervation and L-dopa initiation at a young age contributed to the development of LID; however, the former may be a more important factor.
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spelling pubmed-81553712021-05-28 Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease Nishijima, Haruo Kimura, Tamaki Mori, Fumiaki Wakabayashi, Koichi Kinoshita, Iku Nakamura, Takashi Kon, Tomoya Suzuki, Chieko Tomiyama, Masahiko Front Aging Neurosci Neuroscience BACKGROUND: It remains unclear why patients with young-onset Parkinson’s disease more often develop levo-dihydroxyphenylalanine (L-dopa)-induced dyskinesia (LID) and have a more severe form than patients with old-onset Parkinson’s disease. Previous studies using animal models have failed to show young-onset Parkinson’s disease enhances LID. OBJECTIVES: To evaluate the association of age at dopaminergic denervation (onset age) and initiation of L-dopa treatment (treatment age) with LID development in model rats. METHODS: We established rat models of young- and old-lesioned Parkinson’s disease (6-hydroxydopamine lesions at 10 and 88 weeks of age, respectively). Dopaminergic denervation was confirmed by the rotational behavior test using apomorphine. Rats in the young-lesioned group were allocated to either L-dopa treatment at a young or old age, or saline treatment. Rats in the old-lesioned group were allocated to either L-dopa treatment or saline group. We evaluated L-dopa-induced abnormal involuntary movements during the 14-day treatment period. We also examined preprodynorphin mRNA expression in the striatum (a neurochemical hallmark of LID) and the volume of the medial globus pallidus (a pathological hallmark of LID). RESULTS: LID-like behavior was enhanced in L-dopa-treated young-lesioned rats compared with L-dopa-treated old-lesioned rats. Preprodynorphin mRNA expression was higher in L-dopa-treated young-lesioned rats than in in L-dopa-treated old-lesioned rats. The volume of the medial globus pallidus was greater in L-dopa-treated young-lesioned rats than in L-dopa-treated old-lesioned rats. Treatment age did not affect LID-like behavior or the degree of medial globus pallidus hypertrophy in the young-lesioned model. CONCLUSION: Both dopaminergic denervation and L-dopa initiation at a young age contributed to the development of LID; however, the former may be a more important factor. Frontiers Media S.A. 2021-05-13 /pmc/articles/PMC8155371/ /pubmed/34054505 http://dx.doi.org/10.3389/fnagi.2021.650350 Text en Copyright © 2021 Nishijima, Kimura, Mori, Wakabayashi, Kinoshita, Nakamura, Kon, Suzuki and Tomiyama. 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
Nishijima, Haruo
Kimura, Tamaki
Mori, Fumiaki
Wakabayashi, Koichi
Kinoshita, Iku
Nakamura, Takashi
Kon, Tomoya
Suzuki, Chieko
Tomiyama, Masahiko
Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
title Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
title_full Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
title_fullStr Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
title_full_unstemmed Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
title_short Effects of Aging on Levo-Dihydroxyphenylalanine- Induced Dyskinesia in a Rat Model of Parkinson’s Disease
title_sort effects of aging on levo-dihydroxyphenylalanine- induced dyskinesia in a rat model of parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155371/
https://www.ncbi.nlm.nih.gov/pubmed/34054505
http://dx.doi.org/10.3389/fnagi.2021.650350
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