Project description:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination. Examination of 3 different demyelinating lesions identified by Immunohistopathology.
Project description:Different lesion types were microdissected out from snap-frozen white matter and placed on visium slides. Optimization of RNA release and visualization with Nikon Ecclipse Ti2 were followed by barcoded recover, library preparation and sequencing.
Project description:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination.
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.
Project description:Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS), where ongoing demyelination and remyelination failure are the major factors for progressive neurological disability. In this report, we employed a comprehensive proteomic approach and immunohistochemical (IHC) validation to gaininsight into the pathobiological mechanisms that may be associated with the progressive phase of MS disease. Isolated proteins from myelinated regions, demyelinated white matter lesions (WMLs), and grey-matter lesions (GMLs) of well-characterized progressive MS brain tissues were subjected to label-free quantitative mass spectrometry (LFQ-MS). Using a system-biology approach, we detected increased expression of proteins belonging to mitochondrial electron transport complexes and oxidative phosphorylatio pathway in WMLs. Intriguingly, many of these proteins and pathways had opposite expression patterns in GMLs of progressive MS brains. A comparison to the huma MitoCarta database mapped the mitochondrial proteins to mitochondrial subunits in both WMLs and GMLs. Taken together, we provide evidence of opposite expression of mitochondrial proteins in response to demyelination of white- and grey-matter regions in progressive MS brain.
