Gene expression in cortex and hippocampus during acute pneumococcal meningitis
<p>Abstract</p> <p>Background</p> <p>Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2006-06-01
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| Series: | BMC Biology |
| Online Access: | http://www.biomedcentral.com/1741-7007/4/15 |
| _version_ | 1811277611172626432 |
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| author | Wittwer Matthias Lindberg Raija LP de Saizieu Antoine B Voisin Veronique Coimbra Roney S Leppert David Leib Stephen L |
| author_facet | Wittwer Matthias Lindberg Raija LP de Saizieu Antoine B Voisin Veronique Coimbra Roney S Leppert David Leib Stephen L |
| author_sort | Wittwer Matthias |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown.</p> <p>We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics.</p> <p>Results</p> <p>Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic.</p> <p>Conclusion</p> <p>Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy.</p> |
| first_indexed | 2024-04-13T00:19:51Z |
| format | Article |
| id | doaj.art-14efac364a51460893d07a85dbd08d80 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-13T00:19:51Z |
| publishDate | 2006-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-14efac364a51460893d07a85dbd08d802022-12-22T03:10:48ZengBMCBMC Biology1741-70072006-06-01411510.1186/1741-7007-4-15Gene expression in cortex and hippocampus during acute pneumococcal meningitisWittwer MatthiasLindberg Raija LPde Saizieu Antoine BVoisin VeroniqueCoimbra Roney SLeppert DavidLeib Stephen L<p>Abstract</p> <p>Background</p> <p>Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown.</p> <p>We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics.</p> <p>Results</p> <p>Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic.</p> <p>Conclusion</p> <p>Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy.</p>http://www.biomedcentral.com/1741-7007/4/15 |
| spellingShingle | Wittwer Matthias Lindberg Raija LP de Saizieu Antoine B Voisin Veronique Coimbra Roney S Leppert David Leib Stephen L Gene expression in cortex and hippocampus during acute pneumococcal meningitis BMC Biology |
| title | Gene expression in cortex and hippocampus during acute pneumococcal meningitis |
| title_full | Gene expression in cortex and hippocampus during acute pneumococcal meningitis |
| title_fullStr | Gene expression in cortex and hippocampus during acute pneumococcal meningitis |
| title_full_unstemmed | Gene expression in cortex and hippocampus during acute pneumococcal meningitis |
| title_short | Gene expression in cortex and hippocampus during acute pneumococcal meningitis |
| title_sort | gene expression in cortex and hippocampus during acute pneumococcal meningitis |
| url | http://www.biomedcentral.com/1741-7007/4/15 |
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