Project description:Genome-wide DNA methylation level was studied to determine whether multiple sclerosis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in peripheral blood from multiple sclerosis patients (cases) and normal controls
Project description:In the present study we addressed several questions related to the mechanisms of cortical injury. We analyzed genome wide gene expression by microarrays, comparing active multiple sclerosis lesions with highly inflammatory lesions of chronic tuberculous meningitis, with neurodegenerative lesions of Alzheimer’s disease and with normal cortex of age matched controls. To clarify which inflammatory mediators drive demyelination in the human cortex, we characterized and compared the gene expression profile of cortices derived from patients with progressive Multiple Sclerosis (pMS), Meningitis tuberculosis (MT), Alzheimers disease (AD) as well as of normal cortex from age matched controls. 3 cases of each disease were included into the study. Preceding the gene expression profiling all cases were characterized histologically and areas of interest were identified. RNA was isolated from those areas, amplified and hybridized to Agilent G4112F whole genome microarrays.
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.