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Multiple sclerosis cortical normal-appearing grey matter and control grey matter

ABSTRACT: Multiple sclerosis cortical normal-appearing grey matter and control grey matter

PROVIDER: PRJNA543114 | ENA |

REPOSITORIES: ENA

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Multiple sclerosis cortical normal-appearing grey matter and grey matter lesions

Project description:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the brain. Among characteristics of MS pathology are cortical grey matter abnormalities, which have been linked to clinical signs such as cognitive impairment. To understand MS cortical grey matter lesion pathogenesis, we performed differential gene expression analysis of MS cortical normal-appearing grey matter (NAGM) and grey matter lesions. HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*15:01 cases at the protein level. Analysis of grey matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression. Our data indicate that increased HLA-DRB1 expression in the brain of MS patients may be an important factor in how the HLA-DR15 haplotype contributes to MS risk in the target organ.

2020-01-13 | GSE131279 | GEO

Multiple sclerosis cortical normal-appearing grey matter and control grey matter

Project description:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the brain. Among characteristics of MS pathology are cortical grey matter abnormalities, which have been linked to clinical signs such as cognitive impairment. To understand MS cortical grey matter pathogenesis, we performed differential gene expression analysis of MS normal appearing grey matter (NAGM) and control grey matter. HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*15:01 cases at the protein level. Analysis of grey matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression. Our data indicate that increased HLA-DRB1 expression in the brain of MS patients may be an important factor in how the HLA-DR15 haplotype contributes to MS risk in the target organ.

2020-01-13 | GSE131281 | GEO

Multiple sclerosis cortical normal-appearing grey matter and grey matter lesions

Project description:Multiple sclerosis cortical normal-appearing grey matter and grey matter lesions

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Multiple sclerosis cortical normal-appearing grey matter, grey matter lesions, and control grey matter

Project description:Multiple sclerosis cortical normal-appearing grey matter, grey matter lesions, and control grey matter

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Gene expression of white and grey matter demyelinated areas and normal appearing matter from Multiple Sclerosis leukocortial lesions of human post-mortem tissue

Project description:Using laser capture microscopy, white (WM) and grey matter (GM) demyelinated areas and normal appearing matter was collected from histologically verified leukocortical lesions from snap-frozen human post mortem tissuederived from Multiple Sclerosis patients. Our data shows large differences in gene expression in WM and GM demyelinated areas (compared to their respective normal appearing matter) even when the demyelinated areas are spatially connected such as in leukocortical lesions. Thus, we show that WM demyelinated areas and GM demyelinated areas are distinct entities with distinct pathology. Therefore findings observed in WM demyelinated areas cannot be generalized to GM demyelinated areas.

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Transcriptional profiling of human microglia reveals grey-white matter heterogeneity and multiple sclerosis-associated changes

Project description:Microglia are brain-resident, myelin-phagocytosing cells, yet their role in lesion initiation in grey and white matter regions in multiple sclerosis (MS) is unclear. We isolated primary microglia from both, occipital cortex and corpus callosum, of 10 MS and 11 control donors and studied their transcriptional profile by RNA sequencing, thereby identifying regional and MS-associated changes. Identification of pathways underlying regional differences showed a relatively increased type I interferon response in cortical grey matter microglia, while white matter microglia more highly expressed NF-κB pathway genes. In normal-appearing white matter MS tissue, lipid metabolism genes were increased, suggesting processing of myelin by microglia already in areas seemingly devoid of MS pathology. Normal-appearing grey matter MS microglia showed increased activation of glycolysis and metal ion homeostasis, possibly reflecting microglia reacting to iron depositions. Notably, expression of genes associated with microglia homeostasis were hardly changed, suggesting that subtle regional changes in MS-associated microglia do not yet affect their resting state.

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Transcriptomic analyses of normal-appearing CNS white matter from multiple sclerosis donors reveal subtype-specific molecular signatures of disease

Project description:The transcriptome of normal-appearing white matter for relapse-remitting multiple sclerosis (MS), primary progressive MS and secondary progressive MS was determined using total RNA-sequencing. We then performed a differential gene analysis comparing the normal-appearing white matter for each clinical subtype of MS with non-MS control tissue

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Gene expression profiling of multiple sclerosis brain samples

Project description:Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared to controls.

2019-12-17 | GSE135511 | GEO

Multiple sclerosis cortical normal-appearing grey matter, grey matter lesions, and control grey matter

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-01-13 | GSE131282 | GEO

Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role

Project description:Gene expression profiling has been performed on astrocytes isolated using laser capture microdissection (LCM) from multiple sclerosis normal appearing white matter (NAWM) and control WM to identify whether specific glial changes exist in NAWM which contribute to lesion development or prevent disease progression

2016-09-19 | GSE83670 | GEO

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