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Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo

Motor neuron (MN) loss is the primary pathological hallmark of amyotrophic lateral sclerosis (ALS). Histone deacetylase 4 (HDAC4) is one of several factors involved in nerve–muscle communication during MN loss, hindering muscle reinnervation, as shown in humans and in animal models of ALS, and may e...

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Autores principales: Prior-González, Mara, Lazo-Gómez, Rafael, Tapia, Ricardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581382/
https://www.ncbi.nlm.nih.gov/pubmed/37756598
http://dx.doi.org/10.1242/dmm.049851
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author Prior-González, Mara
Lazo-Gómez, Rafael
Tapia, Ricardo
author_facet Prior-González, Mara
Lazo-Gómez, Rafael
Tapia, Ricardo
author_sort Prior-González, Mara
collection PubMed
description Motor neuron (MN) loss is the primary pathological hallmark of amyotrophic lateral sclerosis (ALS). Histone deacetylase 4 (HDAC4) is one of several factors involved in nerve–muscle communication during MN loss, hindering muscle reinnervation, as shown in humans and in animal models of ALS, and may explain the differential progression observed in patients with ALS – rapid versus slow progression. In this work, we inhibited HDAC4 activity through the administration of a pan-histone deacetylase inhibitor, sodium butyrate, in an in vivo model of chronic spinal MN death induced by AMPA-mediated excitotoxicity. We infused AMPA into the spinal cord at low and high doses, which mimic the rapid and slow progression observed in humans, respectively. We found that muscle HDAC4 expression was increased by high-dose infusion of AMPA. Treatment of animals with sodium butyrate further decreased expression of muscle HDAC4, although non-significantly, and did not prevent the paralysis or the MN loss induced by AMPA infusion. These results inform on the role of muscle HDAC4 in MN degeneration in vivo and provide insights for the search for more suitable therapeutic strategies.
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spelling pubmed-105813822023-10-18 Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo Prior-González, Mara Lazo-Gómez, Rafael Tapia, Ricardo Dis Model Mech Research Article Motor neuron (MN) loss is the primary pathological hallmark of amyotrophic lateral sclerosis (ALS). Histone deacetylase 4 (HDAC4) is one of several factors involved in nerve–muscle communication during MN loss, hindering muscle reinnervation, as shown in humans and in animal models of ALS, and may explain the differential progression observed in patients with ALS – rapid versus slow progression. In this work, we inhibited HDAC4 activity through the administration of a pan-histone deacetylase inhibitor, sodium butyrate, in an in vivo model of chronic spinal MN death induced by AMPA-mediated excitotoxicity. We infused AMPA into the spinal cord at low and high doses, which mimic the rapid and slow progression observed in humans, respectively. We found that muscle HDAC4 expression was increased by high-dose infusion of AMPA. Treatment of animals with sodium butyrate further decreased expression of muscle HDAC4, although non-significantly, and did not prevent the paralysis or the MN loss induced by AMPA infusion. These results inform on the role of muscle HDAC4 in MN degeneration in vivo and provide insights for the search for more suitable therapeutic strategies. The Company of Biologists Ltd 2023-10-13 /pmc/articles/PMC10581382/ /pubmed/37756598 http://dx.doi.org/10.1242/dmm.049851 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Prior-González, Mara
Lazo-Gómez, Rafael
Tapia, Ricardo
Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo
title Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo
title_full Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo
title_fullStr Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo
title_full_unstemmed Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo
title_short Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo
title_sort sodium butyrate does not protect spinal motor neurons from ampa-induced excitotoxic degeneration in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581382/
https://www.ncbi.nlm.nih.gov/pubmed/37756598
http://dx.doi.org/10.1242/dmm.049851
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