Department of Neurobiology, Care Sciences & Society, Division of Neurodegeneration, Karolinska Institutet, Novum, Floor 5, SE-141 86 Stockholm, Sweden.
J Neuroinflammation. 2013 Aug 1;10:99. doi: 10.1186/1742-2094-10-99.
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.
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.
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.
Airway-associated allergy induces changes in brain gene expression toward induction of insulin resistance and inflammatory responses with potential implications for neurodegenerative disorders.
慢性系统性炎症会影响大脑功能，并可能对神经退行性疾病的进展产生负面影响。过敏是一种影响超过 20%的西方人群的慢性炎症性疾病。关于过敏对大脑功能的影响知之甚少。本研究旨在全面了解驱动与慢性气道诱导过敏相关的外周炎症影响大脑的基因。
使用卵清蛋白作为变应原在 C57B/6J 小鼠中诱导气道过敏。在海马体和额叶皮层进行微阵列分析，并与 Affymetrix 相关联。为了进行数据分析，使用主成分分析和正交偏最小二乘判别分析，然后进行途径分析。进行定量聚合酶链反应（qPCR）和蛋白质分析（Western 印迹）以验证微阵列结果。
微阵列分析显示气道相关过敏引起的大脑基因表达的低水平变化。通过途径分析发现，参与抗原加工和呈递、细胞因子-细胞因子相互作用、Toll 样受体和丝裂原活化蛋白激酶信号转导的基因表达发生变化。我们证实了在过敏小鼠的大脑中，胰岛素降解酶的蛋白水平降低，胰岛素受体磷酸化减少。通过 qPCR 还证实了其他过敏诱导的基因表达变化，包括肿瘤坏死因子受体超家族成员 23 和脂多糖结合蛋白水平的增加。
气道相关过敏会引起大脑基因表达的变化，导致胰岛素抵抗和炎症反应的诱导，这可能对神经退行性疾病产生影响。
