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Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice
Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855775/ https://www.ncbi.nlm.nih.gov/pubmed/24324819 http://dx.doi.org/10.1371/journal.pone.0082654 |
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author | d’Errico, Paolo Boido, Marina Piras, Antonio Valsecchi, Valeria De Amicis, Elena Locatelli, Denise Capra, Silvia Vagni, Francesco Vercelli, Alessandro Battaglia, Giorgio |
author_facet | d’Errico, Paolo Boido, Marina Piras, Antonio Valsecchi, Valeria De Amicis, Elena Locatelli, Denise Capra, Silvia Vagni, Francesco Vercelli, Alessandro Battaglia, Giorgio |
author_sort | d’Errico, Paolo |
collection | PubMed |
description | Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients. |
format | Online Article Text |
id | pubmed-3855775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38557752013-12-09 Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice d’Errico, Paolo Boido, Marina Piras, Antonio Valsecchi, Valeria De Amicis, Elena Locatelli, Denise Capra, Silvia Vagni, Francesco Vercelli, Alessandro Battaglia, Giorgio PLoS One Research Article Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients. Public Library of Science 2013-12-06 /pmc/articles/PMC3855775/ /pubmed/24324819 http://dx.doi.org/10.1371/journal.pone.0082654 Text en © 2013 d'Errico et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article d’Errico, Paolo Boido, Marina Piras, Antonio Valsecchi, Valeria De Amicis, Elena Locatelli, Denise Capra, Silvia Vagni, Francesco Vercelli, Alessandro Battaglia, Giorgio Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice |
title | Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice |
title_full | Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice |
title_fullStr | Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice |
title_full_unstemmed | Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice |
title_short | Selective Vulnerability of Spinal and Cortical Motor Neuron Subpopulations in delta7 SMA Mice |
title_sort | selective vulnerability of spinal and cortical motor neuron subpopulations in delta7 sma mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855775/ https://www.ncbi.nlm.nih.gov/pubmed/24324819 http://dx.doi.org/10.1371/journal.pone.0082654 |
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