Identification of central nervous system genes involved in the host response to the scrapie agent.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE1840 | GEO | 2004/10/13
SECONDARY ACCESSION(S): PRJNA90449
REPOSITORIES: GEO
Similar Datasets
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
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
Project description:Sheep scrapie is a transmissible spongiform encephalopathy (TSE), which are invariably fatalM- neurodegenerative diseases of the central nervous system (CNS). Accumulation of the misfolded prion protein, PrPSc in the CNS results in progressive neurodegenerative disease. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with standard scrapie sheep prion (SSBP/1) scrapie by inoculation in the drainage area of the prescapular lymph nodes. PrPSc was consistently detected by immunohistology in the CNS at XX days post infection (dpi). This study compares the genes and physiological pathways that are affected by the progression of TSE disease in the CNS, focusing on time points immediately before (XX dpi) and after (XX dpi) the detection of disease-associated PrPSc.
2014-06-01 | E-MTAB-2369 | biostudies-arrayexpress
Project description:Sheep scrapie is a transmissible spongiform encephalopathy (TSE), which are invariably fatal neurodegenerative diseases of the central nervous system (CNS). Accumulation of the misfolded prion protein, PrPSc in the CNS results in progressive neurodegenerative disease. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes. PrPSc was consistently detected by immunohistology in the CNS at 125 days post infection (dpi). This study compares the genes and physiological pathways that are affected by the progression of TSE disease in the CNS, focusing on time points immediately before (75dpi) and at the time point when PrPSc is consistently detected in the CNS (125 dpi).
2014-06-01 | E-MTAB-2385 | biostudies-arrayexpress
Project description:While prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular. We Adapted RML Mouse Scrapie into Rats and measured the resulting gene expression changes in brain as a result of disease progression. Rats were infected by intracranial inoculation with prion isolates obtained by adaptation of mouse RML scrapie prions into rats. Brain samples were collected from third and fourth passage infected rats and age-matched controls at specified timepoints and gene expression profiles obtained. For each time point, 3 diseased and control brain samples were profiled.
2015-09-01 | E-GEOD-63930 | biostudies-arrayexpress
Project description:MicroRNA alterations were investigated in a Tg501 mouse model of prion disases that express the goat prion protein (PRNP). Age-matched Tg501 mice without inoculation (controls) and intracranially inoculated with caprine scrapie strain were compared in presymptomatic and symptomatic stages.
2020-06-17 | GSE146013 | GEO
Project description:An essential and remarkable process of the biochemical and physiological features in prion diseases is the conversion of a host-encoded prion protein (PrPC) into a misfolded isoform (PrPSc). The conversion of PrPC and the replication of prions, in cases of peripheral infection, occur following the uptake and subsequent spread of prions to brain via spinal cord. We investigated the changes of gene expression profiles in the spleen, cervical spinal cord and thalamus following intraperitoneal inoculation of ME7 scrapie prion and the inter-tissue alterations of the differentially expressed genes through Venn diagram to find genes which are commonly influenced by ME7 scrapie prion spread in the three tissues.
2021-12-31 | GSE157334 | GEO
Project description:Sheep scrapie is a transmissible spongiform encephalopathy (TSE), which are invariably fatal neurodegenerative diseases of the central nervous system (CNS). Accumulation of the misfolded prion protein, PrPSc in the CNS results in progressive neurodegenerative disease. For many transmissible spongiform encephalopathies (TSEs), peripheral lymphoid tissue is an important site of PrPSc amplification but without obvious immunological consequence. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes. PrPSc was consistently detected by immunohistology in these nodes at 50 days post infection (dpi). This study compares the genes and physiological pathways that are affected by the progression of TSE disease in the prescapular lymph nodes, focussing on time points immediately before (10 dpi) and after (50 dpi) the detection of disease-associated PrPSc.
2014-04-06 | E-MTAB-2330 | biostudies-arrayexpress
Project description:Sheep scrapie is a transmissible spongiform encephalopathy (TSE), which are invariably fatal neurodegenerative diseases of the central nervous system (CNS). Accumulation of the misfolded prion protein, PrPSc in the CNS results in progressive neurodegenerative disease. For many transmissible spongiform encephalopathies (TSEs), peripheral lymphoid tissue is an important site of PrPSc amplification but without obvious immunological consequence. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes. PrPSc was consistently detected by immunohistology in these nodes at 50 days post infection (dpi). This study compares the genes and physiological pathways that are affected by the progression of TSE disease in the prescapular lymph nodes, focusing on time points immediately before (10 dpi) and after (50 dpi) the detection of disease-associated PrPSc.
2014-02-20 | E-MTAB-2327 | biostudies-arrayexpress
Project description:Prion infection results in progressive neurodegeneration of the central nervous system invariably resulting in death. The pathological effects of prion diseases in the brain are morphologically well defined, such as gliosis, vacuolation, and the accumulation of disease-specific protease-resistant prion protein (PrPSc). However, the underlying molecular events that lead to the death of neurons are poorly characterised. In this study cDNA microarrays were used to profile gene expression changes in the brains of two different strains of mice infected with three strains of mouse-adapted scrapie. Extensive data was collected and analyzed, from which we identified a core group of 349 prion-related genes (PRGs) that consistently showed altered expression in mouse models. Gene ontology analysis assigned many of the up-regulated genes to functional groups associated with one of the primary neuropathological features of prion diseases, astrocytosis and gliosis; protein synthesis, inflammation, cell proliferation and lipid metabolism. Using a computational tool, Ingenuity Pathway Analysis (IPA), we were able to build networks of interacting genes from the PRG list. The regulatory cytokine TGFB1, involved in modulating the inflammatory response, was identified as the outstanding interaction partner for many of the PRGs. The majority of genes expressed in neurons were down-regulated; a number of these were involved in regulatory pathways including synapse function, calcium signalling, long-term potentiation and ERK/MAPK signalling. Two down-regulated genes coding for the transcription regulators, EGR1 and CREB1, were also identified as central to interacting networks of genes; these factors are often used as markers of neuronal activity and their deregulation could be key to loss of neuronal function. These data provides a comprehensive list of genes that are consistently differentially expressed in multiple scrapie infected mouse models. Building networks of interactions between these genes provides a means to understand the complex interplay in the brain during neurodegeneration. Resolving the key regulatory and signaling events that underlie prion pathogenesis will provide targets for the design of novel therapies and the elucidation of biomarkers. Keywords: disease state analysis C57BL/6 mice were inoculated by intracerebral infection of brain homogenate from mice clinically infected with the ME7, 79a and 22A strains of scrapie. In addition VM mice were also inoculated with the 22A scrapie strain. Mice were sacrificed at the onset of clinical diseases as manifested by uncoordinated gait, flaccid paralysis of the hind limbs, rigidity and abolishment of the righting reflex. Brain tissue was collected from these mice and the RNA isolated. Mouse CNS gene expression was analysed by two-colour microarray experiments using an in house manufactured 11K mouse cDNA microarray. RNA from individual infected mice was hybridized to each array versus pooled reference RNA from an equivalent number of age-matched, mock-infected control mice. In total we hybridized 34 different samples to microarrays in this experiment; 8-10 individual mice from each of the four sample groups were individually processed for separate microarrays. Hierachical clustering shows that the patterns of gene expression are for the most part common to the different mouse models . We used the program EDGE to identify genes that were differentially expressed in mouse brain during clinical disease. We used a P value cut-off of 0.05 as the criteria for selection of significantly differentially expressed genes. A similar design was used to determine gene expression profiles from C57BL/6 mice infected with a fourth strain of scrapie, RML. Total RNA from three mice, plus dye swaps, was hybridized to Agilent whole genome mouse arrays to validate genes identified using our manufactured BMAP arrays.
2010-05-26 | E-GEOD-10310 | biostudies-arrayexpress