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Detection of genome-wide methylation changes in prion-infected central nervous system

ABSTRACT: Detection of genome-wide methylation changes in prion-infected central nervous system

PROVIDER: PRJNA766085 | ENA |

REPOSITORIES: ENA

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Detection of genome-wide methylation changes in prion-infected central nervous system

Project description:Scrapie is a Transmissible Spongiform Encephalopathy (TSE) that affects sheep and goats and it is considered a good natural animal model to study prion diseases. Although changes in DNA methylation occur in many neurodegenerative diseases including human prion diseases, potential DNA methylation alterations have not yet been investigated in the central nervous system (CNS) of any prion disease models or naturally infected cases. We present here a whole genome bisulfite sequencing analysis (WGBS) from thalamus of four naturally scrapie infected sheep and four controls. All animals were female, carried the ARQ/ARQ genotype for the PRNP allele and were sacrificed at similar age (4 to 6 years old). Even if genomes displayed similar average methylation levels, we identified 39 differentially methylated promoters (DMP) and a total of 8,907 differentially methylated regions (DMR). Gene Ontology enrichment revealed that hypomethylated DMRs were enriched in genes involved in transmembrane transport and cell adhesion whereas hypermethylated DMRs were related with intracellular signal transduction genes. Moreover, we compared the set of identified DMRs with genes previously described to be differentially expressed in scrapie and with a set of genes encoding proteins defined to be tenfold more abundant in specific types of CNS cells finding that some of these genes also harboured DMRs. Finally, a validation study using qPCR was conducted showing differences in the expression of five genes (PCDH19, SNCG, WDR45B, PEX1 and CABIN1) that matched the methylation changes observed in the genomic study. Altogether, these findings suggest a potential regulatory role of CNS DNA methylation in prion diseases.

2022-03-10 | GSE184767 | GEO

Identification of central nervous system genes involved in the host response to the scrapie agent.

Project description:In this study we identified genes differentially expressed in the central nervous system (CNS) of mice during infection with mouse-adapted scrapie agents. We used cDNA microarrays to examine gene expression profiles at early, mid (pre-clinical) and late (clinical) time points after inoculation. Keywords = scrapie Keywords = prion Keywords = CNS Keywords = BMAP

2004-10-13 | E-GEOD-1840 | biostudies-arrayexpress

Efavirenz Central Nervous System Side Effects

Project description:Efavirenz Central Nervous System Side Effects

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Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer

Project description:RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for central nervous system cancer or leptomeningeal metastases. PURPOSE: This phase II trial is studying the side effects and how well iodine I 131 monoclonal antibody 3F8 works in treating patients with central nervous system cancer or leptomeningeal cancer.

| 2037925 | ecrin-mdr-crc

Identification of central nervous system genes involved in the host response to the scrapie agent.

2004-10-13 | GSE1840 | GEO

Genomic aberrations in primary central nervous system lymphoma (PCNSL)

Project description:Genomic aberrations in primary central nervous system lymphoma (PCNSL). Two-condition experiment, PCNSLs vs. healthy men. Biological replicates: 12 tumors replicates, 13 peripheral blood replicates.

2010-11-13 | E-GEOD-25298 | biostudies-arrayexpress

Genomic aberrations in primary central nervous system lymphoma (PCNSL)

Project description:Genomic aberrations in primary central nervous system lymphoma (PCNSL).

2010-11-13 | GSE25298 | GEO

Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma

Project description:This SuperSeries is composed of the following subset Series: GSE25297: Genome-wide gene expression comparison (primary central nervous system lymphoma (PCNSL) vs normal lymph node) GSE25298: Genomic aberrations in primary central nervous system lymphoma (PCNSL) Refer to individual Series

2010-11-13 | E-GEOD-25299 | biostudies-arrayexpress

GM-CSF in the central nervous system

Project description:The functional outcome of GM-CSF in the central nervous system

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Astrocyte-Oligodendrocyte interaction regulates central nervous system regeneration

Project description:Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a critical determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.

2023-05-17 | PXD041850 | Pride

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