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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.

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.

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Related in: MedlinePlus

Allergy induces significant changes of gene expression in the mouse brain. Loading plots derived from orthogonal projection to latent structures (OPLS-DA) illustrate a set of genes that significantly contributed to separating allergic mice from control mice (n = 8) with regard to the hippocampus (A) (n = 8) and the frontal cortex (B) (n = 7). The confidence level for each gene is estimated by jackknife algorithm.
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Figure 2: Allergy induces significant changes of gene expression in the mouse brain. Loading plots derived from orthogonal projection to latent structures (OPLS-DA) illustrate a set of genes that significantly contributed to separating allergic mice from control mice (n = 8) with regard to the hippocampus (A) (n = 8) and the frontal cortex (B) (n = 7). The confidence level for each gene is estimated by jackknife algorithm.

Mentions: Multivariate analysis was performed using the SIMCA P + software package (UMETRICS AB, Umeå, Sweden). Principal component analysis (PCA) was used to provide an overview of the data and to detect possible outliers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) [16] was performed to detect genes that significantly differed between allergic and control mice. For this purpose, the data were preprocessed by unit variance scaling and detrending. Variables with a high level of variance are more likely to be expressed than those with a low variance. Therefore, unit variance scaling was selected to scale the data appropriately. This method uses the inverse standard deviation (SD) as a scaling weight for each variable. Detrending improves the interpretability of the data by subtracting variable averages from the data; thus the dataset is repositioned around the origin. The score plots (see Figure 1A through 1D) illustrate the deviation from the center of the model projected on the components (to1, to2, to3, …ton). The variables that are important for the class separation are visualized in the loading plots (see Figure 2A and 2B).


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)

Allergy induces significant changes of gene expression in the mouse brain. Loading plots derived from orthogonal projection to latent structures (OPLS-DA) illustrate a set of genes that significantly contributed to separating allergic mice from control mice (n = 8) with regard to the hippocampus (A) (n = 8) and the frontal cortex (B) (n = 7). The confidence level for each gene is estimated by jackknife algorithm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Allergy induces significant changes of gene expression in the mouse brain. Loading plots derived from orthogonal projection to latent structures (OPLS-DA) illustrate a set of genes that significantly contributed to separating allergic mice from control mice (n = 8) with regard to the hippocampus (A) (n = 8) and the frontal cortex (B) (n = 7). The confidence level for each gene is estimated by jackknife algorithm.
Mentions: Multivariate analysis was performed using the SIMCA P + software package (UMETRICS AB, Umeå, Sweden). Principal component analysis (PCA) was used to provide an overview of the data and to detect possible outliers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) [16] was performed to detect genes that significantly differed between allergic and control mice. For this purpose, the data were preprocessed by unit variance scaling and detrending. Variables with a high level of variance are more likely to be expressed than those with a low variance. Therefore, unit variance scaling was selected to scale the data appropriately. This method uses the inverse standard deviation (SD) as a scaling weight for each variable. Detrending improves the interpretability of the data by subtracting variable averages from the data; thus the dataset is repositioned around the origin. The score plots (see Figure 1A through 1D) illustrate the deviation from the center of the model projected on the components (to1, to2, to3, …ton). The variables that are important for the class separation are visualized in the loading plots (see Figure 2A and 2B).

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