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Chronic airway-induced allergy in mice modifies gene expression in the brain toward insulin resistance and inflammatory responses.

Sarlus H, Wang X, Cedazo-Minguez A, Schultzberg M, Oprica M - J Neuroinflammation (2013)

Bottom Line: The aim of the present study was to obtain a global overview of the genes that drive the effects of peripheral inflammation associated with chronic airway-induced allergy in the brain.Quantitative polymerase chain reaction (qPCR) and protein analysis by Western blotting were performed for the validation of microarray results.We confirmed a reduction of insulin-degrading enzyme at the protein level and a decrease in insulin receptor phosphorylation in the brains of allergic mice.

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Affiliation: Department of Neurobiology, Care Sciences & Society, Division of Neurodegeneration, Karolinska Institutet, Novum, Floor 5, SE-141 86 Stockholm, Sweden. Heela.Sarlus@ki.se

ABSTRACT

Background: Chronic systemic inflammation affects brain functionality and may negatively influence the progression of neurodegenerative disorders. Allergy is a chronic inflammatory disease affecting more than 20% of the Western population. Little is known regarding the influence of allergy on brain functions. The aim of the present study was to obtain a global overview of the genes that drive the effects of peripheral inflammation associated with chronic airway-induced allergy in the brain.

Methods: Airway allergy was induced in C57B/6J mice using ovalbumin as the allergen. Microarray analysis was performed in the hippocampus and frontal cortex in association with Affymetrix. For the data analysis, principal component analysis and orthogonal to latent structures discriminant analysis followed by pathway analysis were used. Quantitative polymerase chain reaction (qPCR) and protein analysis by Western blotting were performed for the validation of microarray results.

Results: Microarray analysis showed low-grade changes in gene expression in the brain induced by airway-associated allergy. Changes in expression were observed for genes involved in antigen processing and presentation, cytokine-cytokine interaction, Toll-like receptor and mitogen-activated protein kinase signaling, as determined by pathway analysis. We confirmed a reduction of insulin-degrading enzyme at the protein level and a decrease in insulin receptor phosphorylation in the brains of allergic mice. Other allergy-induced gene expression changes were confirmed by qPCR, including increased levels of tumor necrosis factor receptor superfamily member 23 and lipopolysaccharide-binding protein.

Conclusion: Airway-associated allergy induces changes in brain gene expression toward induction of insulin resistance and inflammatory responses with potential implications for neurodegenerative disorders.

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Pathway analysis of allergy induced differentially expressed genes in the brain. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis was performed on significantly altered genes between allergic mice and control mice as analysed with orthogonal projection to latent structures discriminant analysis (OPLS-DA). A subset of the significantly enriched pathways is depicted in hippocampus (A) and frontal cortex (B). –pLog value corresponds to the logarithmized hypergeometric p-value adjusted by the multiple test adjustment.
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Figure 4: Pathway analysis of allergy induced differentially expressed genes in the brain. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis was performed on significantly altered genes between allergic mice and control mice as analysed with orthogonal projection to latent structures discriminant analysis (OPLS-DA). A subset of the significantly enriched pathways is depicted in hippocampus (A) and frontal cortex (B). –pLog value corresponds to the logarithmized hypergeometric p-value adjusted by the multiple test adjustment.

Mentions: The analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways in the hippocampus and frontal cortex showed significant enrichment for genes involved in several pathways, as depicted in Figure 4A and 4B. The majority of the indicated pathways were involved in inflammatory responses, such as antigen processing and presentation, Toll-like receptor (TLR) signaling, complement and coagulation cascade, JAK-STAT (Janus kinase and signal transducer and activator of transcription) signaling and cytokine–cytokine interactions. The genes that were altered by allergy in some of the pathways are shown in Additional file 2: Table 3 and Table 4 for hippocampus and frontal cortex, respectively.


Chronic airway-induced allergy in mice modifies gene expression in the brain toward insulin resistance and inflammatory responses.

Sarlus H, Wang X, Cedazo-Minguez A, Schultzberg M, Oprica M - J Neuroinflammation (2013)

Pathway analysis of allergy induced differentially expressed genes in the brain. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis was performed on significantly altered genes between allergic mice and control mice as analysed with orthogonal projection to latent structures discriminant analysis (OPLS-DA). A subset of the significantly enriched pathways is depicted in hippocampus (A) and frontal cortex (B). –pLog value corresponds to the logarithmized hypergeometric p-value adjusted by the multiple test adjustment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750454&req=5

Figure 4: Pathway analysis of allergy induced differentially expressed genes in the brain. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis was performed on significantly altered genes between allergic mice and control mice as analysed with orthogonal projection to latent structures discriminant analysis (OPLS-DA). A subset of the significantly enriched pathways is depicted in hippocampus (A) and frontal cortex (B). –pLog value corresponds to the logarithmized hypergeometric p-value adjusted by the multiple test adjustment.
Mentions: The analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways in the hippocampus and frontal cortex showed significant enrichment for genes involved in several pathways, as depicted in Figure 4A and 4B. The majority of the indicated pathways were involved in inflammatory responses, such as antigen processing and presentation, Toll-like receptor (TLR) signaling, complement and coagulation cascade, JAK-STAT (Janus kinase and signal transducer and activator of transcription) signaling and cytokine–cytokine interactions. The genes that were altered by allergy in some of the pathways are shown in Additional file 2: Table 3 and Table 4 for hippocampus and frontal cortex, respectively.

Bottom Line: The aim of the present study was to obtain a global overview of the genes that drive the effects of peripheral inflammation associated with chronic airway-induced allergy in the brain.Quantitative polymerase chain reaction (qPCR) and protein analysis by Western blotting were performed for the validation of microarray results.We confirmed a reduction of insulin-degrading enzyme at the protein level and a decrease in insulin receptor phosphorylation in the brains of allergic mice.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurobiology, Care Sciences & Society, Division of Neurodegeneration, Karolinska Institutet, Novum, Floor 5, SE-141 86 Stockholm, Sweden. Heela.Sarlus@ki.se

ABSTRACT

Background: Chronic systemic inflammation affects brain functionality and may negatively influence the progression of neurodegenerative disorders. Allergy is a chronic inflammatory disease affecting more than 20% of the Western population. Little is known regarding the influence of allergy on brain functions. The aim of the present study was to obtain a global overview of the genes that drive the effects of peripheral inflammation associated with chronic airway-induced allergy in the brain.

Methods: Airway allergy was induced in C57B/6J mice using ovalbumin as the allergen. Microarray analysis was performed in the hippocampus and frontal cortex in association with Affymetrix. For the data analysis, principal component analysis and orthogonal to latent structures discriminant analysis followed by pathway analysis were used. Quantitative polymerase chain reaction (qPCR) and protein analysis by Western blotting were performed for the validation of microarray results.

Results: Microarray analysis showed low-grade changes in gene expression in the brain induced by airway-associated allergy. Changes in expression were observed for genes involved in antigen processing and presentation, cytokine-cytokine interaction, Toll-like receptor and mitogen-activated protein kinase signaling, as determined by pathway analysis. We confirmed a reduction of insulin-degrading enzyme at the protein level and a decrease in insulin receptor phosphorylation in the brains of allergic mice. Other allergy-induced gene expression changes were confirmed by qPCR, including increased levels of tumor necrosis factor receptor superfamily member 23 and lipopolysaccharide-binding protein.

Conclusion: Airway-associated allergy induces changes in brain gene expression toward induction of insulin resistance and inflammatory responses with potential implications for neurodegenerative disorders.

Show MeSH
Related in: MedlinePlus