Early inflammation and immune response mRNAs in the brain of AD11 anti-NGF mice
Early inflammation and immune response mRNAs in the brain of AD11 anti-NGF mice
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DOI：
10.1016/j.neurobiolaging.2009.05.023
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发表时间：
2011-06-01
影响因子：
4.2
通讯作者：
Cattaneo, Antonino
中科院分区：
文献类型：
--
作者：
D'Onofrio, Mara;Arisi, Ivan;Cattaneo, Antonino
我们在抗 NGF AD11 模型中表征了阿尔茨海默氏症样神经变性早期大脑区域的基因表达谱。从出生后第 30 天 (P30) 和出生后第 90 天 (P90) 小鼠的海马体、皮质和基底前脑中提取总 RNA，并通过微阵列分析研究表达谱，然后对 243 个重要候选者进行 qRT-PCR 验证。基因表达谱的广泛变化已经在 P30 时发生。正如预期的那样，胆碱能系统和神经营养素相关基因的表达发生了改变。有趣的是，受影响最显着的 mRNA 簇与炎症和免疫反应以及 Wnt 信号传导有关。编码不同补体因子的mRNA表现出很大的差异表达。这是值得注意的，因为这些补体级联蛋白参与正常大脑发育和神经退行性疾病期间中枢神经系统突触的消除。这种基因表达模式强调，AD11 神经变性的早期事件以及神经营养缺陷和突触重塑是由炎症反应和大脑免疫营养状态失衡所代表的。这些可能是 AD 发病机制和发展的关键事件。 (C) 2009 Elsevier Inc. 保留所有权利。
We characterized the gene expression profile of brain regions at an early stage of the Alzheimer's like neurodegeneration in the anti-NGF AD11 model. Total RNA was extracted from hippocampus, cortex and basal forebrain of postnatal day 30 (P30) and postnatal day 90 (P90) mice and expression profiles were studied by microarray analysis, followed by qRT-PCR validation of 243 significant candidates. Wide changes in gene expression profiles occur already at P30. As expected, cholinergic system and neurotrophins related genes expression were altered. Interestingly, the most significantly affected clusters of mRNAs are linked to inflammation and immune response, as well as to Wnt signaling. mRNAs encoding for different complement factors show a large differential expression. This is noteworthy, since these complement cascade proteins are involved in CNS synapse elimination, during normal brain developing and in neurodegenerative diseases. This gene expression pattern highlights that an early event in AD11 neurodegeneration is represented, together with neurotrophic deficits and synaptic remodeling, by an inflammatory response and an unbalance in the immunotrophic state of the brain. These might be key events in the pathogenesis and development of AD. (C) 2009 Elsevier Inc. All rights reserved.