S100A9 knockout decreases the memory impairment and neuropathology in crossbreed mice of Tg2576 and S100A9 knockout mice model.
S100A9 knockout decreases the memory impairment and neuropathology in crossbreed mice of Tg2576 and S100A9 knockout mice model.
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DOI：
10.1371/journal.pone.0088924
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Suh YH
中科院分区：
文献类型：
--
作者：
Kim HJ;Chang KA;Ha TY;Kim J;Ha S;Shin KY;Moon C;Nacken W;Kim HS;Suh YH
我们之前的研究表明，炎症相关的S100A9基因在阿尔茨海默病（AD）动物模型和人类AD患者的大脑中显著上调。此外，实验表明，敲低S100A9表达可改善AD模型小鼠（Tg2576）的认知功能，并且这些动物的淀粉样斑块负担减轻。本研究通过将Tg2576小鼠与S100A9敲除（KO）小鼠杂交，建立了一种新的AD转基因动物模型。我们观察到，S100A9KO/Tg2576 （KO/Tg）小鼠在Morris水迷宫任务和y迷宫任务中表现出更高的空间参考记忆，并且由于Aβ水平降低而导致淀粉样蛋白β (Aβ)神经病理学降低。与年龄匹配的S100A9WT/Tg2576 （WT/Tg）小鼠相比，淀粉样蛋白前体蛋白c端片段（APP-CT）和磷酸化tau，抗炎IL-10的表达增加，炎症IL-6和肿瘤神经衰弱因子(TNF)-α的表达降低。总之，这些结果表明S100A9是Tg2576小鼠神经变性和认知缺陷的原因。S100A9的作用机制能够与炎症过程相吻合。这些发现表明，敲除S100A9是阿尔茨海默病药物治疗的潜在靶点。
Our previous study presented evidence that the inflammation-related S100A9 gene is significantly upregulated in the brains of Alzheimer's disease (AD) animal models and human AD patients. In addition, experiments have shown that knockdown of S100A9 expression improves cognition function in AD model mice (Tg2576), and these animals exhibit reduced amyloid plaque burden. In this study, we established a new transgenic animal model of AD by crossbreeding the Tg2576 mouse with the S100A9 knockout (KO) mouse. We observed that S100A9KO/Tg2576 (KO/Tg) mice displayed an increased spatial reference memory in the Morris water maze task and Y-maze task as well as decreased amyloid beta peptide (Aβ) neuropathology because of reduced levels of Aβ, C-terminal fragments of amyloid precursor protein (APP-CT) and phosphorylated tau and increased expression of anti-inflammatory IL-10 and also decreased expression of inflammatory IL-6 and tumor neurosis factor (TNF)-α when compared with age-matched S100A9WT/Tg2576 (WT/Tg) mice. Overall, these results suggest that S100A9 is responsible for the neurodegeneration and cognitive deficits in Tg2576 mice. The mechanism of S100A9 is able to coincide with the inflammatory process. These findings indicate that knockout of S100A9 is a potential target for the pharmacological therapy of AD.
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影响因子：
64.8
作者：
Chen, GQ;Chen, KS;Morris, RGM
通讯作者：
Morris, RGM
影响因子：
6.1
作者：
Almeida, CG;Tampellini, D;Gouras, GK
通讯作者：
Gouras, GK
影响因子：
2.1
作者：
Ferrer, I.;Gomez-Isla, T.;Avila, J.
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Avila, J.
影响因子：
7.7
作者：
Liu, Jialin;Wang, Hailin;Qin, Chuan
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Qin, Chuan
影响因子：
64.8
作者：
Janus, C;Pearson, J;Westaway, D
通讯作者：
Westaway, D