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Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss

Despite the relevant research efforts, the causes of amyotrophic lateral sclerosis (ALS) are still unknown and no effective cure is available. Many authors suggest that ALS is a multi-system disease caused by a network failure instead of a cell-autonomous pathology restricted to motoneurons. Althoug...

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Autores principales: Gulino, Rosario, Vicario, Nunzio, Giunta, Maria A. S., Spoto, Graziana, Calabrese, Giovanna, Vecchio, Michele, Gulisano, Massimo, Leanza, Giampiero, Parenti, Rosalba
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471664/
https://www.ncbi.nlm.nih.gov/pubmed/30917493
http://dx.doi.org/10.3390/ijms20061500
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author Gulino, Rosario
Vicario, Nunzio
Giunta, Maria A. S.
Spoto, Graziana
Calabrese, Giovanna
Vecchio, Michele
Gulisano, Massimo
Leanza, Giampiero
Parenti, Rosalba
author_facet Gulino, Rosario
Vicario, Nunzio
Giunta, Maria A. S.
Spoto, Graziana
Calabrese, Giovanna
Vecchio, Michele
Gulisano, Massimo
Leanza, Giampiero
Parenti, Rosalba
author_sort Gulino, Rosario
collection PubMed
description Despite the relevant research efforts, the causes of amyotrophic lateral sclerosis (ALS) are still unknown and no effective cure is available. Many authors suggest that ALS is a multi-system disease caused by a network failure instead of a cell-autonomous pathology restricted to motoneurons. Although motoneuronal loss is the critical hallmark of ALS given their specific vulnerability, other cell populations, including muscle and glial cells, are involved in disease onset and progression, but unraveling their specific role and crosstalk requires further investigation. In particular, little is known about the plastic changes of the degenerating motor system. These spontaneous compensatory processes are unable to halt the disease progression, but their elucidation and possible use as a therapeutic target represents an important aim of ALS research. Genetic animal models of disease represent useful tools to validate proven hypotheses or to test potential therapies, and the conception of novel hypotheses about ALS causes or the study of pathogenic mechanisms may be advantaged by the use of relatively simple in vivo models recapitulating specific aspects of the disease, thus avoiding the inclusion of too many confounding factors in an experimental setting. Here, we used a neurotoxic model of spinal motoneuron depletion induced by injection of cholera toxin-B saporin in the gastrocnemius muscle to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord. The results showed that, following the lesion, the skeletal muscle became atrophic and displayed electromyographic activity similar to that observed in ALS patients. Moreover, the changes in muscle fiber morphology were different from that observed in ALS models, thus suggesting that some muscular effects of disease may be primary effects instead of being simply caused by denervation. Notably, we found plastic changes in the surviving motoneurons that can produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be at least partially driven by glutamatergic signaling, and astrocytes contacting the surviving motoneurons may support this process.
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spelling pubmed-64716642019-04-26 Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss Gulino, Rosario Vicario, Nunzio Giunta, Maria A. S. Spoto, Graziana Calabrese, Giovanna Vecchio, Michele Gulisano, Massimo Leanza, Giampiero Parenti, Rosalba Int J Mol Sci Article Despite the relevant research efforts, the causes of amyotrophic lateral sclerosis (ALS) are still unknown and no effective cure is available. Many authors suggest that ALS is a multi-system disease caused by a network failure instead of a cell-autonomous pathology restricted to motoneurons. Although motoneuronal loss is the critical hallmark of ALS given their specific vulnerability, other cell populations, including muscle and glial cells, are involved in disease onset and progression, but unraveling their specific role and crosstalk requires further investigation. In particular, little is known about the plastic changes of the degenerating motor system. These spontaneous compensatory processes are unable to halt the disease progression, but their elucidation and possible use as a therapeutic target represents an important aim of ALS research. Genetic animal models of disease represent useful tools to validate proven hypotheses or to test potential therapies, and the conception of novel hypotheses about ALS causes or the study of pathogenic mechanisms may be advantaged by the use of relatively simple in vivo models recapitulating specific aspects of the disease, thus avoiding the inclusion of too many confounding factors in an experimental setting. Here, we used a neurotoxic model of spinal motoneuron depletion induced by injection of cholera toxin-B saporin in the gastrocnemius muscle to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord. The results showed that, following the lesion, the skeletal muscle became atrophic and displayed electromyographic activity similar to that observed in ALS patients. Moreover, the changes in muscle fiber morphology were different from that observed in ALS models, thus suggesting that some muscular effects of disease may be primary effects instead of being simply caused by denervation. Notably, we found plastic changes in the surviving motoneurons that can produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be at least partially driven by glutamatergic signaling, and astrocytes contacting the surviving motoneurons may support this process. MDPI 2019-03-26 /pmc/articles/PMC6471664/ /pubmed/30917493 http://dx.doi.org/10.3390/ijms20061500 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gulino, Rosario
Vicario, Nunzio
Giunta, Maria A. S.
Spoto, Graziana
Calabrese, Giovanna
Vecchio, Michele
Gulisano, Massimo
Leanza, Giampiero
Parenti, Rosalba
Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss
title Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss
title_full Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss
title_fullStr Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss
title_full_unstemmed Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss
title_short Neuromuscular Plasticity in a Mouse Neurotoxic Model of Spinal Motoneuronal Loss
title_sort neuromuscular plasticity in a mouse neurotoxic model of spinal motoneuronal loss
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471664/
https://www.ncbi.nlm.nih.gov/pubmed/30917493
http://dx.doi.org/10.3390/ijms20061500
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