Adult CNS Myelin Enhances Axonal Outgrowth From Neural Stem Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE98974 | GEO | 2018/05/16
REPOSITORIES: GEO
Similar Datasets
Project description: Not available
| S-EPMC8377986 | biostudies-literature
Project description:Rapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. Furthermore, a comprehensive analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode. A light-weight membrane fraction enriched for myelin was purified from mouse brains as described previously (Jahn et al., Neuromethods, 2013). For RNA-Seq, RNA was isolated from myelin of mice from indicated ages.
2016-06-24 | E-GEOD-78151 | biostudies-arrayexpress
Project description:Axonal degeneration determines the clinical outcome of multiple sclerosis (MS), and is thought to result from exposure of denuded axons to immune-mediated damage. We challenge this view after finding in MS and its mouse models that myelin itself increases the risk of axons to degenerate under inflammatory conditions. We propose a model for demyelinating diseases in which for axons that remain myelinated, and thus shielded from the extracellular milieu, dependence from oligodendroglial support turns fatal in an autoimmune disease environment.
2023-05-02 | GSE222063 | GEO
Project description:Knowing the effect of autoimmune CNS-targeting T cells on the expression of neurogenesis-associated genes is essential to understand their putative effect on hippocampal functioning. Here, we used RNA microarray analysis to study the effect of myelin-specific T cells on the gene profile in the dentate gyrus 2 days after a perforant pathway transection, when neural precursor cells are highly proliferating. By the use of Gene Ontology analysis, the MANGO database and the Allan Mouse Brain Atlas, we identified dihydropyrimidinase-like 3 (Dpysl3), due to its expression in the subgranular zone of the dentate gyrus. In situ hybridizations and quantification of Dpysl3 mRNA+ grains in the subgranular zone and granular cell layer showed a significant increase in Dpysl3 mRNA in axonal lesioned compared to control mice, and no effect of the myelin-specific T cells. Dpysl3 mRNA was not expressed in Ki-67 mRNA+ proliferating cells and NeuN mRNA+ mature neurons, but it was expressed in Nestin mRNA+ neural precursor cells and even more so in Dcx mRNA+ migrating neuroblasts. These results suggest that the regulation of Dpysl3 mRNA expression in immature granular neurons is refractory to inflammatory mediators secreted by the myelin-specific T cells, while being highly responsive to neuronal stimuli. Comparable mechanisms may support normal hippocampal functioning in diseases characterized by infiltration of autoimmune CNS-targeting T cells, such as multiple sclerosis.
2017-02-01 | GSE78044 | GEO
Project description:Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. During active multiple sclerosis foamy macrophages and microglia, containing degenerated myelin, are abundantly found in demyelinated areas. Recent studies have described an altered macrophage phenotype after myelin internalization. However, by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression is unclear. Here we demonstrate, by using genome wide gene expression analysis, that myelin-phagocytosing macrophages have an enhanced expression of genes in pathways involved in migration, phagocytosis and inflammation. More interestingly, we show that myelin internalization induces the expression of genes involved in liver X receptor signaling and cholesterol efflux. In vitro validation shows that myelin-phagocytosing macrophages indeed have an increased capacity to dispose intracellular cholesterol. Additionally, myelin suppresses the production of pro-inflammatory mediators, like nitric oxide and IL-6, by macrophages in a similar manner as a liver X receptor agonist. Our data show that myelin modulates the phenotype of macrophages by nuclear receptor activation, which may subsequently affect lesion progression in multiple sclerosis. Rat peritoneal macrophages were left untreated (n=5) or treated with isolated myelin (n=5) for 3 days. Both untreated and myelin-treated macrophages were subsequently stimulated with IFNM-RM-/ and IL1-M-NM-2 for 9 hours.
2012-08-20 | E-GEOD-34811 | biostudies-arrayexpress
Project description:Rapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. Furthermore, a comprehensive analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode.
2016-06-24 | GSE78151 | GEO
Project description:Rapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. By bioinformatic comparison, the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode.
2016-12-31 | GSE76458 | GEO
Project description:Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. During active multiple sclerosis foamy macrophages and microglia, containing degenerated myelin, are abundantly found in demyelinated areas. Recent studies have described an altered macrophage phenotype after myelin internalization. However, by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression is unclear. Here we demonstrate, by using genome wide gene expression analysis, that myelin-phagocytosing macrophages have an enhanced expression of genes in pathways involved in migration, phagocytosis and inflammation. More interestingly, we show that myelin internalization induces the expression of genes involved in liver X receptor signaling and cholesterol efflux. In vitro validation shows that myelin-phagocytosing macrophages indeed have an increased capacity to dispose intracellular cholesterol. Additionally, myelin suppresses the production of pro-inflammatory mediators, like nitric oxide and IL-6, by macrophages in a similar manner as a liver X receptor agonist. Our data show that myelin modulates the phenotype of macrophages by nuclear receptor activation, which may subsequently affect lesion progression in multiple sclerosis.
2012-08-20 | GSE34811 | GEO
Project description:Myelin is required for the function of neuronal axons in the central nervous system, yet the mechanisms supporting myelin health are unclear. Although central nervous system macrophages have been implicated, it is unknown which macrophage populations are involved and which aspects of myelin health they influence. Here, we show that resident microglia are critical for the maintenance of myelin health in adulthood in both mouse and human. We demonstrate that whereas microglia are dispensable for developmental myelin ensheathment, they are required for subsequent regulation of myelin growth and associated cognitive function, and for the preservation of myelin integrity by preventing its degeneration. We discovered that loss of myelin health in the absence of microglia is underpinned by the appearance of a myelinating oligodendrocyte subpopulation with altered lipid metabolism, regulated by a disruption of the TGFβ1-TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions where myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease.
2022-10-16 | GSE215440 | GEO
Project description:While the myelin proteome is well characterized in mice, much less is known about the protein composition of myelin in non-mammalian species such as zebrafish (Danio rerio), despite its increasing popularity as model organism for myelin biology. Here, we assess the proteome of myelin biochemically purified from the brains of adult zebrafish by complementary proteomic approaches for deep qualitative and quantitative coverage. A data-independent acquisition (DIA) workflow with alternating low and elevated energy (MSE) provided the high dynamic range required for correct quantification of highest-abundance proteins. According to this analysis, the predominant Ig-CAM myelin protein zero (MPZ/P0), myelin basic protein (MBP) and the short chain dehydrogenase 36K constitute 12%, 8% and 6% of the total myelin protein, respectively. Combined with data from an ion mobility-enhanced version of the MSE mode (referred to as UDMSE) and from 1D-gel-based proteomic approaches, we provide the most comprehensive proteome resource of zebrafish myelin so far, correlate it with previously established mRNA-abundance profiles, and demonstrate both similarities and heterogeneity of myelin composition between teleost fish and rodents.
2021-03-22 | PXD023037 | Pride