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Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia
BACKGROUND: Accurately assessing promising therapeutic interventions for human diseases depends, in part, on the reproducibility of preclinical disease models. With the development of transgenic mice, the rapid adaptation of a 6-OHDA mouse model of Parkinson’s disease that was originally described f...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374903/ https://www.ncbi.nlm.nih.gov/pubmed/30760214 http://dx.doi.org/10.1186/s12868-019-0487-7 |
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author | Rentsch, Peggy Stayte, Sandy Morris, Gary P. Vissel, Bryce |
author_facet | Rentsch, Peggy Stayte, Sandy Morris, Gary P. Vissel, Bryce |
author_sort | Rentsch, Peggy |
collection | PubMed |
description | BACKGROUND: Accurately assessing promising therapeutic interventions for human diseases depends, in part, on the reproducibility of preclinical disease models. With the development of transgenic mice, the rapid adaptation of a 6-OHDA mouse model of Parkinson’s disease that was originally described for the use in rats has come with a lack of a comprehensive characterization of lesion progression. In this study we therefore first characterised the time course of neurodegeneration in the substantia nigra pars compacta and striatum over a 4 week period following 6-OHDA injection into the medial forebrain bundle of mice. We then utilised the model to assess the anti-dyskinetic efficacy of recombinant activin A, a putative neuroprotectant and anti-inflammatory that is endogenously upregulated during the course of Parkinson’s disease. RESULTS: We found that degeneration of fibers in the striatum was fully established within 1 week following 6-OHDA administration, but that the loss of neurons continued to progress over time, becoming fully established 3 weeks after the 6-OHDA injection. In assessing the anti-dyskinetic efficacy of activin A using this model we found that treatment with activin A did not significantly reduce the severity, or delay the time-of-onset, of dyskinesia. CONCLUSION: First, the current study concludes that a 3 week duration is required to establish a complete lesion of the nigrostriatal tract following 6-OHDA injection into the medial forebrain bundle of mice. Second, we found that activin A was not anti-dyskinetic in this model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12868-019-0487-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6374903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63749032019-02-26 Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia Rentsch, Peggy Stayte, Sandy Morris, Gary P. Vissel, Bryce BMC Neurosci Research Article BACKGROUND: Accurately assessing promising therapeutic interventions for human diseases depends, in part, on the reproducibility of preclinical disease models. With the development of transgenic mice, the rapid adaptation of a 6-OHDA mouse model of Parkinson’s disease that was originally described for the use in rats has come with a lack of a comprehensive characterization of lesion progression. In this study we therefore first characterised the time course of neurodegeneration in the substantia nigra pars compacta and striatum over a 4 week period following 6-OHDA injection into the medial forebrain bundle of mice. We then utilised the model to assess the anti-dyskinetic efficacy of recombinant activin A, a putative neuroprotectant and anti-inflammatory that is endogenously upregulated during the course of Parkinson’s disease. RESULTS: We found that degeneration of fibers in the striatum was fully established within 1 week following 6-OHDA administration, but that the loss of neurons continued to progress over time, becoming fully established 3 weeks after the 6-OHDA injection. In assessing the anti-dyskinetic efficacy of activin A using this model we found that treatment with activin A did not significantly reduce the severity, or delay the time-of-onset, of dyskinesia. CONCLUSION: First, the current study concludes that a 3 week duration is required to establish a complete lesion of the nigrostriatal tract following 6-OHDA injection into the medial forebrain bundle of mice. Second, we found that activin A was not anti-dyskinetic in this model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12868-019-0487-7) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-13 /pmc/articles/PMC6374903/ /pubmed/30760214 http://dx.doi.org/10.1186/s12868-019-0487-7 Text en © The Author(s) 2019 Open AccessThis 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Rentsch, Peggy Stayte, Sandy Morris, Gary P. Vissel, Bryce Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia |
title | Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia |
title_full | Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia |
title_fullStr | Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia |
title_full_unstemmed | Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia |
title_short | Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia |
title_sort | time dependent degeneration of the nigrostriatal tract in mice with 6-ohda lesioned medial forebrain bundle and the effect of activin a on l-dopa induced dyskinesia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374903/ https://www.ncbi.nlm.nih.gov/pubmed/30760214 http://dx.doi.org/10.1186/s12868-019-0487-7 |
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