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Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis

Recent studies have suggested a sexually dimorphic role of spinal glial cells in the maintenance of mechanical hypersensitivity in rodent models of chronic pain. We have used the collagen antibody–induced arthritis (CAIA) mouse model to examine differences between males and females in the context of...

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Autores principales: Fernandez-Zafra, Teresa, Gao, Tianle, Jurczak, Alexandra, Sandor, Katalin, Hore, Zoe, Agalave, Nilesh M., Su, Jie, Estelius, Johanna, Lampa, Jon, Hokfelt, Tomas, Wiesenfeld-Hallin, Zsuzsanna, Xu, Xiaojun, Denk, Franziska, Svensson, Camilla I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319583/
https://www.ncbi.nlm.nih.gov/pubmed/30247264
http://dx.doi.org/10.1097/j.pain.0000000000001394
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author Fernandez-Zafra, Teresa
Gao, Tianle
Jurczak, Alexandra
Sandor, Katalin
Hore, Zoe
Agalave, Nilesh M.
Su, Jie
Estelius, Johanna
Lampa, Jon
Hokfelt, Tomas
Wiesenfeld-Hallin, Zsuzsanna
Xu, Xiaojun
Denk, Franziska
Svensson, Camilla I.
author_facet Fernandez-Zafra, Teresa
Gao, Tianle
Jurczak, Alexandra
Sandor, Katalin
Hore, Zoe
Agalave, Nilesh M.
Su, Jie
Estelius, Johanna
Lampa, Jon
Hokfelt, Tomas
Wiesenfeld-Hallin, Zsuzsanna
Xu, Xiaojun
Denk, Franziska
Svensson, Camilla I.
author_sort Fernandez-Zafra, Teresa
collection PubMed
description Recent studies have suggested a sexually dimorphic role of spinal glial cells in the maintenance of mechanical hypersensitivity in rodent models of chronic pain. We have used the collagen antibody–induced arthritis (CAIA) mouse model to examine differences between males and females in the context of spinal regulation of arthritis-induced pain. We have focused on the late phase of this model when joint inflammation has resolved, but mechanical hypersensitivity persists. Although the intensity of substance P, calcitonin gene–related peptide, and galanin immunoreactivity in the spinal cord was not different from controls, the intensity of microglia (Iba-1) and astrocyte (glial fibrillary acidic protein) markers was elevated in both males and females. Intrathecal administration of the glial inhibitors minocycline and pentoxifylline reversed mechanical thresholds in male, but not in female mice. We isolated resident microglia from the lumbar dorsal horns and observed a significantly lower number of microglial cells in females by flow cytometry analysis. However, although genome-wide RNA sequencing results pointed to several transcriptional differences between male and female microglia, no convincing differences were identified between control and CAIA groups. Taken together, these findings suggest that there are subtle sex differences in microglial expression profiles independent of arthritis. Our experiments failed to identify the underlying mRNA correlates of microglial actions in the late phase of the CAIA model. It is likely that transcriptional changes are either subtle and highly localised and therefore difficult to identify with bulk isolation techniques or that other factors, such as changes in protein expression or epigenetic modifications, are at play.
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spelling pubmed-63195832019-01-18 Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis Fernandez-Zafra, Teresa Gao, Tianle Jurczak, Alexandra Sandor, Katalin Hore, Zoe Agalave, Nilesh M. Su, Jie Estelius, Johanna Lampa, Jon Hokfelt, Tomas Wiesenfeld-Hallin, Zsuzsanna Xu, Xiaojun Denk, Franziska Svensson, Camilla I. Pain Research Paper Recent studies have suggested a sexually dimorphic role of spinal glial cells in the maintenance of mechanical hypersensitivity in rodent models of chronic pain. We have used the collagen antibody–induced arthritis (CAIA) mouse model to examine differences between males and females in the context of spinal regulation of arthritis-induced pain. We have focused on the late phase of this model when joint inflammation has resolved, but mechanical hypersensitivity persists. Although the intensity of substance P, calcitonin gene–related peptide, and galanin immunoreactivity in the spinal cord was not different from controls, the intensity of microglia (Iba-1) and astrocyte (glial fibrillary acidic protein) markers was elevated in both males and females. Intrathecal administration of the glial inhibitors minocycline and pentoxifylline reversed mechanical thresholds in male, but not in female mice. We isolated resident microglia from the lumbar dorsal horns and observed a significantly lower number of microglial cells in females by flow cytometry analysis. However, although genome-wide RNA sequencing results pointed to several transcriptional differences between male and female microglia, no convincing differences were identified between control and CAIA groups. Taken together, these findings suggest that there are subtle sex differences in microglial expression profiles independent of arthritis. Our experiments failed to identify the underlying mRNA correlates of microglial actions in the late phase of the CAIA model. It is likely that transcriptional changes are either subtle and highly localised and therefore difficult to identify with bulk isolation techniques or that other factors, such as changes in protein expression or epigenetic modifications, are at play. Wolters Kluwer 2019-01 2018-12-28 /pmc/articles/PMC6319583/ /pubmed/30247264 http://dx.doi.org/10.1097/j.pain.0000000000001394 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Fernandez-Zafra, Teresa
Gao, Tianle
Jurczak, Alexandra
Sandor, Katalin
Hore, Zoe
Agalave, Nilesh M.
Su, Jie
Estelius, Johanna
Lampa, Jon
Hokfelt, Tomas
Wiesenfeld-Hallin, Zsuzsanna
Xu, Xiaojun
Denk, Franziska
Svensson, Camilla I.
Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
title Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
title_full Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
title_fullStr Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
title_full_unstemmed Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
title_short Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
title_sort exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319583/
https://www.ncbi.nlm.nih.gov/pubmed/30247264
http://dx.doi.org/10.1097/j.pain.0000000000001394
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