Sequencing of microglia during focal remyelination of the corpus callosum
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118450 | GEO | 2019/05/24
REPOSITORIES: GEO
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Project description:Sequencing of microglia during focal remyelination of the corpus callosum
| PRJNA485693 | ENA
Project description:Mouse cuprizone (CPZ ) model of experimental de- and remyelination was applied to mimic demyelination pathology of multiple sclerosis. In order to identify differentially expressed microRNAs involved in de- and remyelination, the affected areas of corpus callosum were isolated from mice exposed to CPZ and conducted an Agilent microarray analysis. To induce demyelination, CPZ was administrated for four weeks. Spontaneous remyelination occurs as mice returned to the regular diet after four weeks feeding with CPZ (DEM_4w). Remyelination was examined at two time points: acute remyelination induced by four weeks CPZ feeding followed by two days of regular diet (two days remyelination: REM_2d), and full remyelination induced by four weeks CPZ feeding followed by two weeks of regular diet (two weeks remyelination: REM_2w). Control mice (C) were kept on a normal diet. The following groups representing de- and remyelinisation pathology in corpus callosum of CPZ-treated mice were compared: Demyelination: 4weeks CPZ: DEM_4w; Acute remyelination: 4 weeks CPZ +2 days UNTREATED: REM_2d; Full remyelination: 4 weeks CPZ +2 weeks UNTREATED: REM_2w; and UNTREATED control (C). The experiments were performed using 2-4 animals per groups.
2018-04-11 | GSE100662 | GEO
Project description:To determine expression profiles of cytokines and growth factor profiles in the subventricular zone (SVZ) after demyelination we performed gene array analysis. In SVZ after 4 days post lesin (dpl) LPC-injected tissue, demonstrated regulation of BMP pathway elements, including increased chordin, noggin, and ChorR, and decreased BMP4, compared to NaCl-injected tissue.
2010-04-13 | GSE21310 | GEO
Project description:This study investigated the effect of Vagus Nerve Stimulation (VNS) on innate neuroinflammation and remyelination in lysolecithin (LPC) induced demyelination, a preclinical model for Multiple Sclerosis (MS). In a first experiment (demyelination experiment), LPC was injected in the corpus callosum of 33 Lewis rats, inducing a demyelinated lesion, and rats were treated with either continuously-cycled VNS (cVNS) or one-minute per day VNS (1minVNS) or sham VNS, from two days before the injection until three days post-injection (dpi), when they were killed for immunohistochemistry and proteomics analysis. This timepoint corresponded with a demyelinated lesion and peak inflammation. In a second experiment (remyelination experiment), 13 rats were analogously treated with either cVNS or sham from two days before LPC injection until 11 dpi, when they were killed for tissue prelevation for immunohistochemistry and proteomics. This timepoints corresponded with partial remyelination of the lesion. For proteomics analysis, 20 rats were randomly selected, namely five cVNS and five sham rats of the demyelination experiment, and five cVNS and five sham rats of the remyelination experiment.
2024-05-10 | PXD050858 | Pride
Project description:Remyelination failure contributes to axonal dysfunction in neurodegenerative disorders. But whether astrocytes, the most abundant glial cell type in demyelinated lesions, support or impede remyelination is controversial. Following focal demyelinated lesions of the mouse corpus callosum induced with the myelin toxin lysolecithin, we used TRAP (translational ribosome affinity purification) sequencing to isolate and sequence ribosome-associated mRNAs which are being actively translated in astrocytes, and studied how the responses and molecular mechanisms in astrocytes are linked to remyelination.
2023-05-17 | E-MTAB-9270 | biostudies-arrayexpress
Project description:To determine expression profiles of cytokines and growth factor profiles in the subventricular zone (SVZ) after demyelination we performed gene array analysis. In SVZ after 4 days post lesin (dpl) LPC-injected tissue, demonstrated regulation of BMP pathway elements, including increased chordin, noggin, and ChorR, and decreased BMP4, compared to NaCl-injected tissue. GEArrayTM expression array systems (cat#OMM031 SuperArray, Bethesda, MD) consisted of spotted cDNA fragments encoding 113 mouse genes for neurotrophic signaling molecules involved in neuronal growth and differentiation, as well as regeneration and survival. Control sequences (PUC18, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), peptidylpropyl isomerase A (Ppia), and ?-actin) were also included. These microarrays were employed to compare SVZ gene expression 4 days after NaCl or LPC injection in corpus callosum. Total RNA was isolated by Trizol (Invitrogen) and processed for microarray hybridization following the manufacturer’s instructions. Arrays were visualized by autoradiography, and hybridization signals were scanned and analyzed for density in GEArray Expression Analysis Suite 2.0. The normalized value for each gene was calculated by dividing the value of each gene by the average value of the housekeeping genes GAPDH, Ppia, and ?-actin.
2010-04-13 | E-GEOD-21310 | biostudies-arrayexpress
Project description:Remyelination is reparative process by which axons that have lost their supportive insulation are re-encased in myelin. Multiple cell types are known to participate in this process, but their transcriptional dynamics from initial injury to full repair remain poorly characterized. Here, we combined high-throughput single-nucleus RNA-seq with Slide-seq, a high-resolution spatial transcriptomics technology, to densely reconstruct the cellular processes that coordinate remyelination after lysolecithin injection. First, we found extensive transcriptional diversity of glia and monocyte-derived macrophages from damage to repair. Second, we identified a population of infiltrating peripheral immune cells-- mostly CD8 T-cells and natural killer cells--that are enriched specifically during remyelination. Thirdly, we identified a concerted Interferon-response signature that is shared across several glial cell types--microglia, astrocytes, and oligodendrocyte lineage--just prior to reestablishment of myelin
2024-09-09 | GSE276570 | GEO
Project description:AimExperimental studies have shown that the progesterone metabolite, allopregnanolone, is endowed with promyelinating effects. The mechanisms underlying these promyelinating effects are not well understood. Therefore, we explored the impact of allopregnanolone's synthetic analogue, ganaxolone, on remyelination and microglial activation following focal demyelination in the corpus callosum of ovariectomized rats.MethodsOvariectomized adult Sprague Dawley rats received a stereotaxic injection of 2 µL of 1% lysolecithin solution in the corpus callosum followed by daily injections of either ganaxolone (intraperitoneal injection [i.p.], 2.5 mg/kg) or vehicle. The demyelination lesion was assessed 3 and 7 days postdemyelination insult using Luxol fast blue staining and transmission electron microscopy. The expression levels of myelin proteins (MBP, MAG, MOG, CNPase) were explored using Western blot. The inflammatory response and clearance of damaged myelin were evaluated using immunofluorescent staining (Iba1, dMBP, GFAP) and multiplex enzyme-linked immunosorbent assay (IL-1β, TNF-α, IL-4, IL-10, IL-6).ResultsSystemic administration of ganaxolone promoted remyelination of lysolecithin-induced demyelination, upregulated the expression of major myelin proteins, and enhanced microglial clearance of damaged myelin. Astrocytosis, as well as locally produced pro- and antiinflammatory cytokines, was not affected by ganaxolone treatment.ConclusionGanaxolone promotes remyelination in response to focal demyelination of the corpus callosum of ovariectomized rats. This effect is, at least in part, mediated by enhancing microglial clearance of myelin debris, which creates a conducive environment for a successful remyelination process.
| S-EPMC6978248 | biostudies-literature
Project description:Microglia are strongly implicated in demyelinating neurodegenerative diseases with increasing evidence for roles in protection and healing, but the mechanisms that control CNS remyelination are poorly understood. Here we show that microglia-specific deletion of TNFR1 and pharmacological inhibition of soluble TNF (solTNF) or downstream IL-1R allow maturation of highly activated disease-associated microglia with increased size and myelin phagocytosis capacity that accelerate cortical remyelination and motor recovery. Single cell transcriptomic analysis of cortex at disease onset reveal that solTNF inhibition enhances reparative IL-10-responsive, while preventing damaging IL-1-related signatures of disease-associated microglia. Longitudinal brain transcriptome analysis through disease reveal earlier recovery upon therapeutic loss of microglia TNFR1. Functional relevance of microglia inflammatory polarization pathways for disease is validated in vivo. Furthermore, disease-state microglia producing downstream IL-1/IL-18/NLRP3/CASP1 targets are identified in human demyelinating lesions. Overall, redirecting disease microglia polarization by targeting cytokines is a potential approach for improving CNS repair in demyelinating disorders.
2024-11-12 | GSE278199 | GEO
Project description:Microglia are strongly implicated in demyelinating neurodegenerative diseases with increasing evidence for roles in protection and healing, but the mechanisms that control CNS remyelination are poorly understood. Here we show that microglia-specific deletion of TNFR1 and pharmacological inhibition of soluble TNF (solTNF) or downstream IL-1R allow maturation of highly activated disease-associated microglia with increased size and myelin phagocytosis capacity that accelerate cortical remyelination and motor recovery. Single cell transcriptomic analysis of cortex at disease onset reveal that solTNF inhibition enhances reparative IL-10-responsive, while preventing damaging IL-1-related signatures of disease-associated microglia. Longitudinal brain transcriptome analysis through disease reveal earlier recovery upon therapeutic loss of microglia TNFR1. Functional relevance of microglia inflammatory polarization pathways for disease is validated in vivo. Furthermore, disease-state microglia producing downstream IL-1/IL-18/NLRP3/CASP1 targets are identified in human demyelinating lesions. Overall, redirecting disease microglia polarization by targeting cytokines is a potential approach for improving CNS repair in demyelinating disorders.
2024-11-12 | GSE278137 | GEO