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

Research output: Contribution to journalArticlepeer-review

Teresa Fernandez-Zafra, Tianle Gao, Alexandra Jurczak, Katalin Sandor, Zoe Hore, Nilesh M Agalave, Jie Su, Johanna Estelius, Jon Lampa, Tomas Hokfelt, Zsuzsanna Wiesenfeld-Hallin, Xiaojun Xu, Franziska Denk, Camilla I Svensson

Original languageEnglish
Pages (from-to)224-236
Issue number1
Early online date27 Aug 2018
Accepted/In press17 Aug 2018
E-pub ahead of print27 Aug 2018
PublishedJan 2019


King's Authors


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. While the intensity of substance P, CGRP and galanin immunoreactivity in the spinal cord was not different from controls, the intensity of microglia (Iba-1) and astrocyte (GFAP) markers was elevated in both males and females. Intrathecal administration of the glial inhibitors minocycline and pentoxifylline reversed mechanical thresholds in male, but not 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, while 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.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The work cannot be changed in any way or used commercially without permission from the journal.

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