Gene expression in cortex and hippocampus during acute pneumococcal meningitis

Coimbra, Roney S.; Voisin, Veronique; de Saizieu, Antoine B.; Lindberg, Raija L. P.; Wittwer, Matthias; Leppert, David; Leib, Stephen L. (2006). Gene expression in cortex and hippocampus during acute pneumococcal meningitis. BMC biology, 4, p. 15. London: BioMed Central 10.1186/1741-7007-4-15

[img]
Preview
Text
1741-7007-4-15.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (1MB) | Preview

BACKGROUND: Pneumococcal meningitis is associated with high mortality (approximately 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.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. RESULTS: Among 598 genes differentially regulated (change factor > or = 1.5; p < or = 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. CONCLUSION: Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Leib, Stephen

ISSN:

1741-7007

ISBN:

16749930

Publisher:

BioMed Central

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:46

Last Modified:

05 Dec 2022 14:14

Publisher DOI:

10.1186/1741-7007-4-15

PubMed ID:

16749930

Web of Science ID:

000239301400001

BORIS DOI:

10.7892/boris.19178

URI:

https://boris.unibe.ch/id/eprint/19178 (FactScience: 1599)

Actions (login required)

Edit item Edit item
Provide Feedback