Profiling the microRNA signature of the peripheral sensory ganglia in experimental autoimmune encephalomyelitis (EAE)

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.

Exosomal miR-23a-3p derived from human umbilical cord mesenchymal stem cells promotes remyelination in central nervous system demyelinating diseases by targeting Tbr1/Wnt pathway

“…Studies have identified certain miRNAs with high abundance in MSCs-Exos that possess unique immunomodulatory effects and are involved in myelin damage and regeneration associated with MS. Examples include miR-122 ( 42 ), miR-21 ( 42 , 43 ), miR-146a ( 44 ), miR-24 ( 45 ), and miR-223 ( 45 , 46 ). To investigate the impact of HUMSCs-Exos on OPC differentiation and maturation, we performed transcriptome sequencing to identify DEGs between HUMSCs-Exos-treated OPCs and untreated OPCs.…”

Sex differences in the inflammatory response of the mouse DRG and its connection to pain in experimental autoimmune encephalomyelitis

“…Our lab has shown previously that TNFα is increased peripherally in circulating immune cells in EAE 12 . To confirm this result in our current tissue set, we assessed TNFα levels in the male and female EAE DRG by polymerase chain reaction (PCR) using previously described methods 38 . We found TNFα mRNA is elevated in both sexes in EAE (Supplementary Fig.…”

Social Isolation and Enrichment Induce Unique miRNA Signatures in the Prefrontal Cortex and Behavioral Changes in Mice

“…Overall, our work provide experimental evidence supporting the link between environmental modifications, behavioral changes and precise miRNAs profiles in the mouse PFC. Specific miRNA signatures have been consistently found in multiple brain conditions ( Belzeaux et al., 2018 ; Burns et al., 2018 ; Friedman et al., 2019 ; Leidinger et al., 2013 ), and their understanding and manipulation would be extremely useful for clinical purposes.…”