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Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice

BACKGROUND: Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria...

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Autores principales: Delahaye, Nicolas F, Coltel, Nicolas, Puthier, Denis, Barbier, Mathieu, Benech, Philippe, Joly, Florence, Iraqi, Fuad A, Grau, Georges E, Nguyen, Catherine, Rihet, Pascal
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246131/
https://www.ncbi.nlm.nih.gov/pubmed/18062806
http://dx.doi.org/10.1186/1471-2164-8-452
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author Delahaye, Nicolas F
Coltel, Nicolas
Puthier, Denis
Barbier, Mathieu
Benech, Philippe
Joly, Florence
Iraqi, Fuad A
Grau, Georges E
Nguyen, Catherine
Rihet, Pascal
author_facet Delahaye, Nicolas F
Coltel, Nicolas
Puthier, Denis
Barbier, Mathieu
Benech, Philippe
Joly, Florence
Iraqi, Fuad A
Grau, Georges E
Nguyen, Catherine
Rihet, Pascal
author_sort Delahaye, Nicolas F
collection PubMed
description BACKGROUND: Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (CM-R) and CM-susceptible (CM-S) mice, upon infection by Plasmodium berghei ANKA (PbA). We investigated mouse transcriptional responses at early and late stages of infection by use of cDNA microarrays. RESULTS: Through a rigorous statistical approach with multiple testing corrections, we showed that PbA significantly altered brain gene expression in CM-R (BALB/c), and in CM-S (CBA/J and C57BL/6) mice, and that 327 genes discriminated between early and late infection stages, between mouse strains, and between CM-R and CM-S mice. We further identified 104, 56, 84 genes with significant differential expression between CM-R and CM-S mice on days 2, 5, and 7 respectively. The analysis of their functional annotation indicates that genes involved in metabolic energy pathways, the inflammatory response, and the neuroprotection/neurotoxicity balance play a major role in cerebral malaria pathogenesis. In addition, our data suggest that cerebral malaria and Alzheimer's disease may share some common mechanisms of pathogenesis, as illustrated by the accumulation of β-amyloid proteins in brains of CM-S mice, but not of CM-R mice. CONCLUSION: Our microarray analysis highlighted marked changes in several molecular pathways in CM-S compared to CM-R mice, particularly at early stages of infection. This study revealed some promising areas for exploration that may both provide new insight into the knowledge of CM pathogenesis and the development of novel therapeutic strategies.
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spelling pubmed-22461312008-02-19 Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice Delahaye, Nicolas F Coltel, Nicolas Puthier, Denis Barbier, Mathieu Benech, Philippe Joly, Florence Iraqi, Fuad A Grau, Georges E Nguyen, Catherine Rihet, Pascal BMC Genomics Research Article BACKGROUND: Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (CM-R) and CM-susceptible (CM-S) mice, upon infection by Plasmodium berghei ANKA (PbA). We investigated mouse transcriptional responses at early and late stages of infection by use of cDNA microarrays. RESULTS: Through a rigorous statistical approach with multiple testing corrections, we showed that PbA significantly altered brain gene expression in CM-R (BALB/c), and in CM-S (CBA/J and C57BL/6) mice, and that 327 genes discriminated between early and late infection stages, between mouse strains, and between CM-R and CM-S mice. We further identified 104, 56, 84 genes with significant differential expression between CM-R and CM-S mice on days 2, 5, and 7 respectively. The analysis of their functional annotation indicates that genes involved in metabolic energy pathways, the inflammatory response, and the neuroprotection/neurotoxicity balance play a major role in cerebral malaria pathogenesis. In addition, our data suggest that cerebral malaria and Alzheimer's disease may share some common mechanisms of pathogenesis, as illustrated by the accumulation of β-amyloid proteins in brains of CM-S mice, but not of CM-R mice. CONCLUSION: Our microarray analysis highlighted marked changes in several molecular pathways in CM-S compared to CM-R mice, particularly at early stages of infection. This study revealed some promising areas for exploration that may both provide new insight into the knowledge of CM pathogenesis and the development of novel therapeutic strategies. BioMed Central 2007-12-06 /pmc/articles/PMC2246131/ /pubmed/18062806 http://dx.doi.org/10.1186/1471-2164-8-452 Text en Copyright © 2007 Delahaye et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Delahaye, Nicolas F
Coltel, Nicolas
Puthier, Denis
Barbier, Mathieu
Benech, Philippe
Joly, Florence
Iraqi, Fuad A
Grau, Georges E
Nguyen, Catherine
Rihet, Pascal
Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice
title Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice
title_full Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice
title_fullStr Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice
title_full_unstemmed Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice
title_short Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice
title_sort gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246131/
https://www.ncbi.nlm.nih.gov/pubmed/18062806
http://dx.doi.org/10.1186/1471-2164-8-452
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