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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse cerebral malaria susceptible and resistant animals

ABSTRACT: Cerebral malaria (CM) is a leading cause of death in the world. Better understanding of the pathogenesis of this disease is critical for the development of novel therapies. In this work, we investigated temporal gene expression profiles in the brains of CM-susceptible and CM-resistant mice during infection with P. Berghia ANKA (PbA). In this model of CM, susceptible mice develop neurological signs by day 6 post infection while resistant mice do not develop neurological manifestations during malarial infection. Experiment Overall Design: C57/B6 (CM-susceptible) and Balb/C (CM-resistant) mice were infected with PbA. Gene expression profiles from whole brains were obtained at day 0 (uninfected), day 1, day 3, and day 6.

ORGANISM(S): Mus musculus

SUBMITTER: Sina Gharib

PROVIDER: E-GEOD-7814 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Expression microarray analysis implicates apoptosis and interferon-responsive mechanisms in susceptibility to experimental cerebral malaria.

Lovegrove Fiona E FE Gharib Sina A SA Patel Samir N SN Hawkes Cheryl A CA Kain Kevin C KC Liles W Conrad WC

The American journal of pathology 20071108 6

Specific local brain responses, influenced by parasite sequestration and host immune system activation, have been implicated in the development of cerebral malaria. This study assessed whole-brain transcriptional responses over the course of experimental cerebral malaria by comparing genetically resistant and susceptible inbred mouse strains infected with Plasmodium berghei ANKA. Computational methods were used to identify differential patterns of gene expression. Overall, genes that showed the ...[more]

PMID: 17991715

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Transcriptional Profiling of Cerebral Malaria

Project description:Cerebral malaria (CM) is a leading cause of death in the world. Better understanding of the pathogenesis of this disease is critical for the development of novel therapies. In this work, we investigated temporal gene expression profiles in the brains of CM-susceptible and CM-resistant mice during infection with P. Berghia ANKA (PbA). In this model of CM, susceptible mice develop neurological signs by day 6 post infection while resistant mice do not develop neurological manifestations during malarial infection. Keywords: Time course

2007-10-01 | GSE7814 | GEO

Distinct pathways of pathogenesis in mice with experimental cerebral malaria following P. berghei ANKA infection.

2007-10-11 | GSE6019 | GEO

Transcription profiling of brain tissue from cerebral malaria-resistant and susceptible strains of mice in a time series following infection with Plasmodium berghei

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2007-05-01 | E-MEXP-1018 | biostudies-arrayexpress

Transcription profiling of mouse with experimental cerebral malaria following P. berghei ANKA infection.

Project description:Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, predominantly experienced by children and non-immune adults, which results in great mortality and long-term sequelae. Recent reports based on histology of post-mortem brain tissue suggest that CM may be the common end point for a range of syndromes. Here, we have analysed the gene expression profiles in brain tissue taken from experimental CM (ECM)-susceptible, Plasmodium berghei ANKA (PbA)-infected C57BL/6 (B6) and CBA/CaH (CBA) mice with ECM. Gene expression profiles were largely heterogeneous between the two ECM-susceptible strains. These results, combined with experimental data, support the existence of distinct pathogenic pathways in CM. Experiment Overall Design: C57BL/6 and CBA/CaH mice were infected with 10e5 Plasmodium berghei ANKA-infected RBCs and monitored for ECM development. At onset of ECM symptoms, infected mice and naive controls were culled, perfused (in order to remove non-adherent circulating cells), and brains were removed. Total RNA was extracted from these brains and pooled (n=6 mice/ group). Pooled RNA samples were converted to cDNA and antisense cRNA, labelled and hybridized to GeneChip Mouse Genome 430 2.0 Arrays (Affymetrix, Surrey Hills, Australia). Arrays were scanned using the GeneChip Scanner 3000 (Affymetrix) and GeneChip Operating Software v1.1.1 (Affymetrix). Normalisation and initial analyses were carried out in GeneSpring v7 (Agilent Technologies). Values below 0.01 were set to 0.01. Each measurement was divided by the 50th percentile of all measurements in that sample. The data was filtered for genes flagged as present, which had at least an expression level of 50. Following this, a threshold of 2.5 fold up-regulation or down-regulation of genes differentially expressed during ECM was set.

2008-06-14 | E-GEOD-6019 | biostudies-arrayexpress

Simultaneous Host and Parasite Expression Profiling Identifies Transcriptional Programs Associated with Cerebral Malaria

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Predominance of interferon-related responses in the brain during murine malaria as identified by microarray analysis.

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2008-03-14 | E-GEOD-9808 | biostudies-arrayexpress

Splenic CD4 T cells in naïve C57BL/6 mice or during Plasmodium berghei ANKA infection in C57BL/6 and B6.GzmB-/- mice.

Project description:Infection of C57BL/6 mice with Plasmodium berghei ANKA (PbA) is a well-established experimental model of cerebral malaria (ECM). ECM is characterised by high levels of parasite sequestration and recruitment of pathogenic CD8+ T cells to the brain. The role of CD4+ T cells in this model has not yet been fully elucidated, although our laboratory has recently shown that CD4+ T cell depletion prior to infection results in significantly lower parasite burdens and protection from ECM. These data highlight a pathogenic role for CD4+ T cells in ECM. Our unpublished observations indicate that mice lacking the CD8+ T cell cytolytic effector molecule, Granzyme B, (GzmB), are resistant to ECM, showing markedly reduced parasite burdens. Late depletion of CD4+ T cells from PbA-infected GzmB-deficient mice results in enhanced parasite burdens, indicating that these cells may play an anti-parasitic role. In the present study, we have analysed splenic CD4+ T cell gene expression profiles in naïve C57BL/6 mice, and PbA-infected wild-type and GzmB-deficent mice to further our understanding of the CD4+ T cell response in ECM. Splenic CD4 T cells isolated by cell sorting from either uninfected C57BL/6 or PbA-infected C57BL/6 or B6.GzmB-/- mice at day 4 post-infection. Total RNA obtained from four mice per group.

2010-12-10 | E-GEOD-24903 | biostudies-arrayexpress

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