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首页> 外文期刊>Journal of neuroinflammation >Chronic airway-induced allergy in mice modifies gene expression in the brain toward insulin resistance and inflammatory responses
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Chronic airway-induced allergy in mice modifies gene expression in the brain toward insulin resistance and inflammatory responses

机译：小鼠慢性气道诱发的过敏改变大脑中针对胰岛素抵抗和炎症反应的基因表达

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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.
机译：背景慢性全身性炎症会影响大脑功能，并可能对神经退行性疾病的发展产生负面影响。过敏是一种慢性炎症性疾病，影响了超过20％的西方人口。关于过敏对脑功能的影响知之甚少。本研究的目的是获得驱动与慢性气道诱发的大脑过敏相关的周围炎症影响的基因的全球概况。方法以卵清蛋白为过敏原，诱导C57B / 6J小鼠气道过敏。与Affymetrix联合在海马和额叶皮层中进行微阵列分析。对于数据分析，使用主成分分析和与潜在结构正交的判别分析，然后进行路径分析。进行定量聚合酶链反应（qPCR）和蛋白质印迹分析，以验证微阵列结果。结果芯片分析显示，气道相关过敏导致大脑基因表达的低级变化。通过途径分析确定，观察到了涉及抗原加工和呈递，细胞因子-细胞因子相互作用，Toll样受体和有丝分裂原激活的蛋白激酶信号转导的基因表达的变化。我们证实了变应性小鼠大脑中蛋白质水平上胰岛素降解酶的减少和胰岛素受体磷酸化的减少。 qPCR证实了其他变态反应诱导的基因表达变化，包括增加的肿瘤坏死因子受体超家族成员23和脂多糖结合蛋白的水平。结论气道相关过敏可诱导脑基因表达的变化，从而诱导胰岛素抵抗和炎症反应，可能对神经退行性疾病有潜在影响。

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