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Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model
Chronic administration of L-DOPA, the first-line treatment of dystonic symptoms in childhood or in Parkinson’s disease, often leads to the development of abnormal involuntary movements (AIMs), which represent an important clinical problem. Although it is known that Riluzole attenuates L-DOPA-induced...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647536/ https://www.ncbi.nlm.nih.gov/pubmed/30484112 http://dx.doi.org/10.1007/s12035-018-1433-x |
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author | Pagliaroli, Luca Widomska, Joanna Nespoli, Ester Hildebrandt, Tobias Barta, Csaba Glennon, Jeffrey Hengerer, Bastian Poelmans, Geert |
author_facet | Pagliaroli, Luca Widomska, Joanna Nespoli, Ester Hildebrandt, Tobias Barta, Csaba Glennon, Jeffrey Hengerer, Bastian Poelmans, Geert |
author_sort | Pagliaroli, Luca |
collection | PubMed |
description | Chronic administration of L-DOPA, the first-line treatment of dystonic symptoms in childhood or in Parkinson’s disease, often leads to the development of abnormal involuntary movements (AIMs), which represent an important clinical problem. Although it is known that Riluzole attenuates L-DOPA-induced AIMs, the molecular mechanisms underlying this effect are not understood. Therefore, we studied the behavior and performed RNA sequencing of the striatum in three groups of rats that all received a unilateral lesion with 6-hydroxydopamine in their medial forebrain bundle, followed by the administration of saline, L-DOPA, or L-DOPA combined with Riluzole. First, we provide evidence that Riluzole attenuates AIMs in this rat model. Subsequently, analysis of the transcriptomics data revealed that Riluzole is predicted to reduce the activity of CREB1, a transcription factor that regulates the expression of multiple proteins that interact in a molecular landscape involved in apoptosis. Although this mechanism underlying the beneficial effect of Riluzole on AIMs needs to be confirmed, it provides clues towards novel or existing compounds for the treatment of AIMs that modulate the activity of CREB1 and, hence, its downstream targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1433-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6647536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-66475362019-08-06 Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model Pagliaroli, Luca Widomska, Joanna Nespoli, Ester Hildebrandt, Tobias Barta, Csaba Glennon, Jeffrey Hengerer, Bastian Poelmans, Geert Mol Neurobiol Original Paper Chronic administration of L-DOPA, the first-line treatment of dystonic symptoms in childhood or in Parkinson’s disease, often leads to the development of abnormal involuntary movements (AIMs), which represent an important clinical problem. Although it is known that Riluzole attenuates L-DOPA-induced AIMs, the molecular mechanisms underlying this effect are not understood. Therefore, we studied the behavior and performed RNA sequencing of the striatum in three groups of rats that all received a unilateral lesion with 6-hydroxydopamine in their medial forebrain bundle, followed by the administration of saline, L-DOPA, or L-DOPA combined with Riluzole. First, we provide evidence that Riluzole attenuates AIMs in this rat model. Subsequently, analysis of the transcriptomics data revealed that Riluzole is predicted to reduce the activity of CREB1, a transcription factor that regulates the expression of multiple proteins that interact in a molecular landscape involved in apoptosis. Although this mechanism underlying the beneficial effect of Riluzole on AIMs needs to be confirmed, it provides clues towards novel or existing compounds for the treatment of AIMs that modulate the activity of CREB1 and, hence, its downstream targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1433-x) contains supplementary material, which is available to authorized users. Springer US 2018-11-27 2019 /pmc/articles/PMC6647536/ /pubmed/30484112 http://dx.doi.org/10.1007/s12035-018-1433-x Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Paper Pagliaroli, Luca Widomska, Joanna Nespoli, Ester Hildebrandt, Tobias Barta, Csaba Glennon, Jeffrey Hengerer, Bastian Poelmans, Geert Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model |
title | Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model |
title_full | Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model |
title_fullStr | Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model |
title_full_unstemmed | Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model |
title_short | Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity: Insights from a Rat Model |
title_sort | riluzole attenuates l-dopa-induced abnormal involuntary movements through decreasing creb1 activity: insights from a rat model |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647536/ https://www.ncbi.nlm.nih.gov/pubmed/30484112 http://dx.doi.org/10.1007/s12035-018-1433-x |
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