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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

Confirmation of allergy induced changes in gene expression by quantitative PCR. RNA was reverse-transcribed and probed for the tumor necrosis factor receptor superfamily member 23 (TNFRS23) in the hippocampus (A) and lipopolysaccharide-binding protein (LPB) in the frontal cortex (B). The qPCR results are in accord with the data obtained from microarray analysis. The data were analyzed using Student’s t-test. The boxplot indicates the first two quartiles with the median, and the whiskers indicate the third and fourth quartiles (n = 8 mice per group). Asterisk, p< 0.05, triple asterisk, p< 0.001. AU, arbitrary units.
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Figure 7: Confirmation of allergy induced changes in gene expression by quantitative PCR. RNA was reverse-transcribed and probed for the tumor necrosis factor receptor superfamily member 23 (TNFRS23) in the hippocampus (A) and lipopolysaccharide-binding protein (LPB) in the frontal cortex (B). The qPCR results are in accord with the data obtained from microarray analysis. The data were analyzed using Student’s t-test. The boxplot indicates the first two quartiles with the median, and the whiskers indicate the third and fourth quartiles (n = 8 mice per group). Asterisk, p< 0.05, triple asterisk, p< 0.001. AU, arbitrary units.

Mentions: We have further validated other significant changes provided by the microarray analysis with qPCR for TNFRS23 in the hippocampus (Figure 7A) and LBP in the frontal cortex (Figure 7B). The results were in line with the microarray data. Thus, the levels of TNFRS23 were increased in the hippocampus of allergic mice [95% CI −0.82- −0.31; P < 0.001] and LBP levels were increased in the frontal cortex [95% CI −0.49 - −0.04; P < 0.05].


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)

Confirmation of allergy induced changes in gene expression by quantitative PCR. RNA was reverse-transcribed and probed for the tumor necrosis factor receptor superfamily member 23 (TNFRS23) in the hippocampus (A) and lipopolysaccharide-binding protein (LPB) in the frontal cortex (B). The qPCR results are in accord with the data obtained from microarray analysis. The data were analyzed using Student’s t-test. The boxplot indicates the first two quartiles with the median, and the whiskers indicate the third and fourth quartiles (n = 8 mice per group). Asterisk, p< 0.05, triple asterisk, p< 0.001. AU, arbitrary units.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Confirmation of allergy induced changes in gene expression by quantitative PCR. RNA was reverse-transcribed and probed for the tumor necrosis factor receptor superfamily member 23 (TNFRS23) in the hippocampus (A) and lipopolysaccharide-binding protein (LPB) in the frontal cortex (B). The qPCR results are in accord with the data obtained from microarray analysis. The data were analyzed using Student’s t-test. The boxplot indicates the first two quartiles with the median, and the whiskers indicate the third and fourth quartiles (n = 8 mice per group). Asterisk, p< 0.05, triple asterisk, p< 0.001. AU, arbitrary units.
Mentions: We have further validated other significant changes provided by the microarray analysis with qPCR for TNFRS23 in the hippocampus (Figure 7A) and LBP in the frontal cortex (Figure 7B). The results were in line with the microarray data. Thus, the levels of TNFRS23 were increased in the hippocampus of allergic mice [95% CI −0.82- −0.31; P < 0.001] and LBP levels were increased in the frontal cortex [95% CI −0.49 - −0.04; P < 0.05].

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