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Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease
Musculoskeletal chronic pain is prevalent in individuals with Alzheimer’s disease (AD); however, it remains largely untreated in these patients, raising the possibility that pain mechanisms are perturbed. Here, we utilise the TASTPM transgenic mouse model of AD with the K/BxN serum transfer model of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287730/ https://www.ncbi.nlm.nih.gov/pubmed/37349313 http://dx.doi.org/10.1038/s41467-023-39077-1 |
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author | Sideris-Lampretsas, George Oggero, Silvia Zeboudj, Lynda Silva, Rita Bajpai, Archana Dharmalingam, Gopuraja Collier, David A. Malcangio, Marzia |
author_facet | Sideris-Lampretsas, George Oggero, Silvia Zeboudj, Lynda Silva, Rita Bajpai, Archana Dharmalingam, Gopuraja Collier, David A. Malcangio, Marzia |
author_sort | Sideris-Lampretsas, George |
collection | PubMed |
description | Musculoskeletal chronic pain is prevalent in individuals with Alzheimer’s disease (AD); however, it remains largely untreated in these patients, raising the possibility that pain mechanisms are perturbed. Here, we utilise the TASTPM transgenic mouse model of AD with the K/BxN serum transfer model of inflammatory arthritis. We show that in male and female WT mice, inflammatory allodynia is associated with a distinct spinal cord microglial response characterised by TLR4-driven transcriptional profile and upregulation of P2Y12. Dorsal horn nociceptive afferent terminals release the TLR4 ligand galectin-3 (Gal-3), and intrathecal injection of a Gal-3 inhibitor attenuates allodynia. In contrast, TASTPM mice show reduced inflammatory allodynia, which is not affected by the Gal-3 inhibitor and correlates with the emergence of a P2Y12(−) TLR4(−) microglia subset in the dorsal horn. We suggest that sensory neuron-derived Gal-3 promotes allodynia through the TLR4-regulated release of pro-nociceptive mediators by microglia, a process that is defective in TASTPM due to the absence of TLR4 in a microglia subset. |
format | Online Article Text |
id | pubmed-10287730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102877302023-06-24 Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease Sideris-Lampretsas, George Oggero, Silvia Zeboudj, Lynda Silva, Rita Bajpai, Archana Dharmalingam, Gopuraja Collier, David A. Malcangio, Marzia Nat Commun Article Musculoskeletal chronic pain is prevalent in individuals with Alzheimer’s disease (AD); however, it remains largely untreated in these patients, raising the possibility that pain mechanisms are perturbed. Here, we utilise the TASTPM transgenic mouse model of AD with the K/BxN serum transfer model of inflammatory arthritis. We show that in male and female WT mice, inflammatory allodynia is associated with a distinct spinal cord microglial response characterised by TLR4-driven transcriptional profile and upregulation of P2Y12. Dorsal horn nociceptive afferent terminals release the TLR4 ligand galectin-3 (Gal-3), and intrathecal injection of a Gal-3 inhibitor attenuates allodynia. In contrast, TASTPM mice show reduced inflammatory allodynia, which is not affected by the Gal-3 inhibitor and correlates with the emergence of a P2Y12(−) TLR4(−) microglia subset in the dorsal horn. We suggest that sensory neuron-derived Gal-3 promotes allodynia through the TLR4-regulated release of pro-nociceptive mediators by microglia, a process that is defective in TASTPM due to the absence of TLR4 in a microglia subset. Nature Publishing Group UK 2023-06-22 /pmc/articles/PMC10287730/ /pubmed/37349313 http://dx.doi.org/10.1038/s41467-023-39077-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sideris-Lampretsas, George Oggero, Silvia Zeboudj, Lynda Silva, Rita Bajpai, Archana Dharmalingam, Gopuraja Collier, David A. Malcangio, Marzia Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease |
title | Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease |
title_full | Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease |
title_fullStr | Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease |
title_full_unstemmed | Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease |
title_short | Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease |
title_sort | galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287730/ https://www.ncbi.nlm.nih.gov/pubmed/37349313 http://dx.doi.org/10.1038/s41467-023-39077-1 |
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