RNA-seq analysis of anti-malarial drug chemotherapy of murine experimental Cerebral Malaria (ECM)
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PROVIDER: PRJEB24903 | ENA |
REPOSITORIES: ENA
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Project description:Cerebral Malaria (HCM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently the only treatment for HCM is the provision of anti-malarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify new potential adjunct treatments for HCM, we performed a non-biased whole brain transcriptomic time-course analysis of anti-malarial drug chemotherapy of murine experimental CM (ECM).
2018-07-03 | E-MTAB-6474 | biostudies-arrayexpress
Project description:Cerebral malaria (CM) is one of the most severe complications of malaria infection. There is evidence that repeated parasite exposure promotes resistance against CM, as indicated by the low incidence of CM in adults in malaria-endemic regions. However, the immunological basis of this infection-induced resistance remains poorly understood. Here, a microarray study done utilising the tractable Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we show that three rounds of infection and drug-cure protects against the development of ECM during a subsequent fourth infection.
2019-02-19 | E-MTAB-5513 | biostudies-arrayexpress
Project description:Cerebral malaria is a pathology involving inflammation in the brain. There are many immune cell types activated during this process, but there is little information on the contribution of microglia, the brain resident macrophages, to this severe complication. We have examined the responses of microglia in a model of experimental cerebral malaria (ECM), in which C57BL/6 mice are infected with Plasmodium berghei ANKA. Genome wide transcriptomic analysis of these cells revealed that thousands of transcripts were differentially expressed at two different time points during the infection. The analysis indicated that proliferation of microglia was a dominant feature before the onset of ECM, and supporting this, we observed an increase in numbers of these cells in the brain. When cerebral malaria symptoms were manifest, genes involved in immune responses and chemokine production were upregulated, which were possibly driven by Type I Interferon. Together, our data offer a unique insight into the responses of microglia in the brain during ECM.
2016-12-19 | GSE86082 | GEO
Project description:We found that oral activated charcoal (oAC) provided significant protection against P. berghei ANKA-induced ECM, significantly increasing overall survival time compared to untreated mice. Protection from ECM by oAC was associated with a reduced numbers of splenic TNF+ CD4+ T cells and multifunctional IFNy+TNF+ CD4+ and CD8+ T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, a group of female C57BL/6 mice infected with PbA received Activated Charcoal. At day 6 p.i., and prior to the first deaths of untreated PbA-infected mice, 5 untreated PbA-infected mice (Group 1) and 5 AC-treated PbA-infected mice (Group 2) were killed and fresh blood (300-500�l per mouse) was collected and processed into RNA. Blood was also taken from uninfected control mice (�baseline�- Group 3).
2010-04-01 | E-MEXP-2594 | biostudies-arrayexpress
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
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
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. Keywords: disease state analysis
2007-10-11 | GSE6019 | GEO
Project description:Purpose:This study aimed to investigate the transcriptome-wide response of experimental cerebral malaria (ECM) and artesunate treated mice brain on 6 days post-infection. Methods: C57BL/6 mice were infected with Plasmodium berghei ANKA to construct a murine ECM in MB and AB group. AB group treated with artesunate (30mg/kg), while CB group treated with PBS for 4 days. Mice brain was tested by RNA-seq. Results: Gene ontology and KEGG pathway analyses of differentially expressed genes (DEGs) were performed. quantitative reverse transcription polymerase chain reaction (qPCR) verify DEGs such as Il6, Il1b, Il10, Tnf, Ifng, Il21, Icam1, which were up-regulated in MB vs. CB, while down-regulated in AB vs. MB. Conclusions:Our study revealed a transcriptome-wide profile in ECM and artesunate treated mice brain, and help to explore the underlying mechanism, as well as the further development of therapeutic strategies for clinical cerebral malaria.
2022-12-02 | GSE162535 | GEO
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. 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.
2008-06-15 | E-GEOD-7814 | biostudies-arrayexpress
Project description:Cerebral malaria (CM) is a severe complication of a Plasmodium falciparum infection and is still responsible for a high number of deaths and long term disabilities in children in sub-Saharan Africa. The pathogenesis of this syndrome remains incompletely understood but a number of mechanisms and effectors have been proposed, including plasma microparticles (MP). These submicron vesicles released by potentially all cells carry proteins and nucleic acids derived from the mother cell. In CM, their numbers are increased in patients’ circulation and, in the mouse model, they can be localised within inflamed vessels, suggesting their involvement in vascular damage. In the present work we define, for the first time, the protein cargo of MP during experimental cerebral malaria (ECM) with the overarching hypothesis that characterising this content could help in better understand CM pathogenesis. Using qualitative and quantitative high-throughput proteomics we compared MP proteins from non-infected mice and mice infected with P. berghei ANKA at two different stages of infection, i.e., pre-clinical phase and full blown syndrome. Overall, we identified 368 proteins, 60 of which were differentially expressed, as determined by quantitative comparison using the TMT® isobaric labelling. The analysis with Ingenuity® IPA highlighted important networks significantly represented among the proteins over-expressed (n=42) or identified only (n=21) in ECM, comprising mechanisms already proposed to be involved in CM, such as endothelial activation. Two proteins of interest, carbonic anhydrase I (CA-I) and S100A8, were verified by western blot on newly collected MP samples from DBA/1 (n=16) and C57BL/6 (n=8) mice, and confirmed to be associated with ECM MP. These results demonstrate that MP protein cargo represents a novel ECM pathogenic trait to consider in the understanding of CM pathogenesis. The identification of the cellular source of MP containing proteins associated to the disease state will contribute to further understanding their involvement in CM.
2016-12-13 | PXD003772 | Pride