Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury
Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury
SUMMARY Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis and in vitro primary cultures of microglia to characterize the sex differences in microglia in pain-related regions in nerve injury and chemotherapy-induced peripheral neuropathy mouse models. Whilst mechanical allodynia and behavioral changes were observed in all models, transcriptomic analysis revealed a substantial change in microglial gene expression only within the ipsilateral lumbar spinal cord 7-days after nerve injury. Both sexes upregulated genes associated with inflammation, phagosome, and lysosome activation, though males revealed a prominent global transcriptional shift not observed in female mice, reflecting acute activation. Further, in vitro studies revealed that only male microglia from nerve-injured mice developed a reactive phenotype with increased phagocytotic activity. This study indicates distinct sex differences in spinal microglia and suggests they contribute to the sex-specific pain processing following nerve injury.
Hayes Jessica、Fiore Nathan T、Gauthier Christian D、Butovsky Oleg、Yin Zhuoran、Guneykaya Dilansu、Moalem-Taylor Gila、D?ˉHary Aaron
Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South WalesTranslational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South WalesAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women?ˉs Hospital, Harvard Medical SchoolAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women?ˉs Hospital, Harvard Medical School||Evergrande Center for Immunologic Diseases, Brigham and Women?ˉs Hospital, Harvard Medical SchoolAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women?ˉs Hospital, Harvard Medical SchoolAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women?ˉs Hospital, Harvard Medical SchoolTranslational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South WalesTranslational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales
基础医学神经病学、精神病学生物科学研究方法、生物科学研究技术
microglianeuropathic painnerve injurychemotherapy-induced peripheral neuropathysex
Hayes Jessica,Fiore Nathan T,Gauthier Christian D,Butovsky Oleg,Yin Zhuoran,Guneykaya Dilansu,Moalem-Taylor Gila,D?ˉHary Aaron.Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.05.27.446082.点此复制
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