Abstract
BackgroundMultiple sclerosis is an autoimmune disease with a distinct female bias, as well as a high prevalence of neuropathic pain in both sexes. The dorsal root ganglia (DRG) contain the primary sensory neurons that give rise to pain, and damage to these neurons may lead to neuropathic pain. Here, we investigate the sex differences of the DRG transcriptome in a mouse model of MS.MethodsNext-generation sequencing was used to establish RNA and microRNA profiles from the DRG of mice with MOG35–55-induced EAE, a model of CNS inflammation that mimics aspects of MS. Differential expression and multiple meta-analytic approaches were used to compare expression profiles in immunized female and male mice. Differential expression of relevant genes and microRNAs were confirmed by qPCR.ResultsThree thousand five hundred twenty genes and 29 microRNAs were differentially expressed in the DRG of female mice with MOG35–55-EAE, while only 189 genes and 3 microRNAs were differentially expressed in males with MOG35–55-EAE. Genes related to the immune system were uniquely regulated in immunized female mice. Direct comparison of sex within disease indicates significant differences in interferon and phagosomal pathways between the sexes. miR-21a-5p is the primary dysregulated microRNA in both sexes, with females having additional dysregulated microRNAs, including miR-122-5p.ConclusionsThis study provides evidence that females are uniquely affected by MOG35–55-EAE and that this difference may result from additional signaling not present in the male. The altered transcriptome of females correlates with other studies finding hyperactivity of pain-sensing neurons and suggests underlying sex-specific pathways for neuropathic pain.
Highlights
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination, disturbances in neuronal function, and progressive neurodegeneration [1]
Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS, where an autoimmune response is artificially induced against the myelin of the central
While transcriptome dysregulation has been studied in the Central nervous system (CNS) and immune cell populations in the context of EAE [7,8,9], less research has been done on the peripheral nervous system (PNS), a potential source of neuropathic pain in the disease
Summary
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination, disturbances in neuronal function, and progressive neurodegeneration [1]. While transcriptome dysregulation has been studied in the CNS and immune cell populations in the context of EAE [7,8,9], less research has been done on the PNS, a potential source of neuropathic pain in the disease. Our laboratory has described differences in the development of pain states between female and male mice in the EAE model. These differences include differences in immune and neurodegenerative histochemical and oxidative stress profiles [2, 4]. Knowing that sex differences exist in EAE and that there are functional alterations correlated to pain, we sought to describe the transcriptional profile of the DRG in EAE from female and male mice with the disease. We investigate the sex differences of the DRG transcriptome in a mouse model of MS
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