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Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS
Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motone...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922970/ https://www.ncbi.nlm.nih.gov/pubmed/29580378 http://dx.doi.org/10.7554/eLife.30955 |
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author | Martínez-Silva, María de Lourdes Imhoff-Manuel, Rebecca D Sharma, Aarti Heckman, CJ Shneider, Neil A Roselli, Francesco Zytnicki, Daniel Manuel, Marin |
author_facet | Martínez-Silva, María de Lourdes Imhoff-Manuel, Rebecca D Sharma, Aarti Heckman, CJ Shneider, Neil A Roselli, Francesco Zytnicki, Daniel Manuel, Marin |
author_sort | Martínez-Silva, María de Lourdes |
collection | PubMed |
description | Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motoneurons to display the strongest hyperexcitability prior to their degeneration, whereas the less vulnerable should display a moderate hyperexcitability, if any. We tested this hypothesis in vivo in two unrelated ALS mouse models by correlating the electrical properties of motoneurons with their physiological types, identified based on their motor unit contractile properties. We found that, far from being hyperexcitable, the most vulnerable motoneurons become unable to fire repetitively despite the fact that their neuromuscular junctions were still functional. Disease markers confirm that this loss of function is an early sign of degeneration. Our results indicate that intrinsic hyperexcitability is unlikely to be the cause of motoneuron degeneration. |
format | Online Article Text |
id | pubmed-5922970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59229702018-04-30 Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS Martínez-Silva, María de Lourdes Imhoff-Manuel, Rebecca D Sharma, Aarti Heckman, CJ Shneider, Neil A Roselli, Francesco Zytnicki, Daniel Manuel, Marin eLife Neuroscience Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motoneurons to display the strongest hyperexcitability prior to their degeneration, whereas the less vulnerable should display a moderate hyperexcitability, if any. We tested this hypothesis in vivo in two unrelated ALS mouse models by correlating the electrical properties of motoneurons with their physiological types, identified based on their motor unit contractile properties. We found that, far from being hyperexcitable, the most vulnerable motoneurons become unable to fire repetitively despite the fact that their neuromuscular junctions were still functional. Disease markers confirm that this loss of function is an early sign of degeneration. Our results indicate that intrinsic hyperexcitability is unlikely to be the cause of motoneuron degeneration. eLife Sciences Publications, Ltd 2018-03-27 /pmc/articles/PMC5922970/ /pubmed/29580378 http://dx.doi.org/10.7554/eLife.30955 Text en © 2018, Martínez-Silva et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Martínez-Silva, María de Lourdes Imhoff-Manuel, Rebecca D Sharma, Aarti Heckman, CJ Shneider, Neil A Roselli, Francesco Zytnicki, Daniel Manuel, Marin Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title | Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_full | Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_fullStr | Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_full_unstemmed | Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_short | Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS |
title_sort | hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of als |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922970/ https://www.ncbi.nlm.nih.gov/pubmed/29580378 http://dx.doi.org/10.7554/eLife.30955 |
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