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Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions

Age‐induced degeneration of the neuromuscular junction (NMJ) is associated with motor dysfunction and muscle atrophy. While the impact of aging on the NMJ presynapse and postsynapse is well‐documented, little is known about the changes perisynaptic Schwann cells (PSCs), the synaptic glia of the NMJ,...

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Autores principales: Hastings, Robert Louis, Avila, Mary Flordelys, Suneby, Emma, Juros, Devin, O'Young, Anson, Peres da Silva, Jason, Valdez, Gregorio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652323/
https://www.ncbi.nlm.nih.gov/pubmed/37771191
http://dx.doi.org/10.1111/acel.13981
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author Hastings, Robert Louis
Avila, Mary Flordelys
Suneby, Emma
Juros, Devin
O'Young, Anson
Peres da Silva, Jason
Valdez, Gregorio
author_facet Hastings, Robert Louis
Avila, Mary Flordelys
Suneby, Emma
Juros, Devin
O'Young, Anson
Peres da Silva, Jason
Valdez, Gregorio
author_sort Hastings, Robert Louis
collection PubMed
description Age‐induced degeneration of the neuromuscular junction (NMJ) is associated with motor dysfunction and muscle atrophy. While the impact of aging on the NMJ presynapse and postsynapse is well‐documented, little is known about the changes perisynaptic Schwann cells (PSCs), the synaptic glia of the NMJ, undergo during aging. Here, we examined PSCs in young, middle‐aged, and old mice in three muscles with different susceptibility to aging. Using light and electron microscopy, we found that PSCs acquire age‐associated cellular features either prior to or at the same time as the onset of NMJ degeneration. Notably, we found that aged PSCs fail to completely cap the NMJ even though they are more abundant in old compared with young mice. We also found that aging PSCs form processes that either intrude into the synaptic cleft or guide axonal sprouts to innervate other NMJs. We next profiled the transcriptome of PSCs and other Schwann cells (SCs) to identify mechanisms altered in aged PSCs. This analysis revealed that aged PSCs acquire a transcriptional pattern previously shown to promote phagocytosis that is absent in other SCs. It also showed that aged PSCs upregulate unique pro‐inflammatory molecules compared to other aged SCs. Interestingly, neither synaptogenesis genes nor genes that are typically upregulated by repair SCs were induced in aged PSCs or other SCs. These findings provide insights into cellular and molecular mechanisms that could be targeted in PSCs to stave off the deleterious effects of aging on NMJs.
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spelling pubmed-106523232023-09-28 Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions Hastings, Robert Louis Avila, Mary Flordelys Suneby, Emma Juros, Devin O'Young, Anson Peres da Silva, Jason Valdez, Gregorio Aging Cell Research Articles Age‐induced degeneration of the neuromuscular junction (NMJ) is associated with motor dysfunction and muscle atrophy. While the impact of aging on the NMJ presynapse and postsynapse is well‐documented, little is known about the changes perisynaptic Schwann cells (PSCs), the synaptic glia of the NMJ, undergo during aging. Here, we examined PSCs in young, middle‐aged, and old mice in three muscles with different susceptibility to aging. Using light and electron microscopy, we found that PSCs acquire age‐associated cellular features either prior to or at the same time as the onset of NMJ degeneration. Notably, we found that aged PSCs fail to completely cap the NMJ even though they are more abundant in old compared with young mice. We also found that aging PSCs form processes that either intrude into the synaptic cleft or guide axonal sprouts to innervate other NMJs. We next profiled the transcriptome of PSCs and other Schwann cells (SCs) to identify mechanisms altered in aged PSCs. This analysis revealed that aged PSCs acquire a transcriptional pattern previously shown to promote phagocytosis that is absent in other SCs. It also showed that aged PSCs upregulate unique pro‐inflammatory molecules compared to other aged SCs. Interestingly, neither synaptogenesis genes nor genes that are typically upregulated by repair SCs were induced in aged PSCs or other SCs. These findings provide insights into cellular and molecular mechanisms that could be targeted in PSCs to stave off the deleterious effects of aging on NMJs. John Wiley and Sons Inc. 2023-09-28 /pmc/articles/PMC10652323/ /pubmed/37771191 http://dx.doi.org/10.1111/acel.13981 Text en © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Hastings, Robert Louis
Avila, Mary Flordelys
Suneby, Emma
Juros, Devin
O'Young, Anson
Peres da Silva, Jason
Valdez, Gregorio
Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions
title Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions
title_full Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions
title_fullStr Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions
title_full_unstemmed Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions
title_short Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions
title_sort cellular and molecular evidence that synaptic schwann cells contribute to aging of mouse neuromuscular junctions
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652323/
https://www.ncbi.nlm.nih.gov/pubmed/37771191
http://dx.doi.org/10.1111/acel.13981
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