Altered expression and distribution of zinc transporters in APP/PS1 transgenic mouse brain
Altered expression and distribution of zinc transporters in APP/PS1 transgenic mouse brain
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DOI：
10.1016/j.neurobiolaging.2008.02.018
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发表时间：
2010-01
影响因子：
4.2
通讯作者：
Li-hong Zhang;Xin Wang;Zhi-hong Zheng;Hao Ren;M. Stoltenberg;G. Danscher;Liping Huang;Ming Rong-Min
中科院分区：
文献类型：
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作者：
Li-hong Zhang;Xin Wang;Zhi-hong Zheng;Hao Ren;M. Stoltenberg;G. Danscher;Liping Huang;Ming Rong-Min
β-淀粉样肽（Aβ）的病理性蓄积是阿尔茨海默病（AD）的早期和常见特征。增加锌浓度可启动Aβ沉积。本研究旨在研究锌转运蛋白（ZnT）家族的6个成员ZnT 1、ZnT 3、ZnT 4、ZnT 5、ZnT 6和ZnT 7在APPswe/PS1 dE 9转基因小鼠脑中的表达和分布模式。结果显示，在海马和新皮层中，ZnT 1、ZnT 3、ZnT 4、ZnT 6和ZnT 7的表达均显著增加（P<0.05），而在斑块和淀粉样血管病变血管中，锌离子的分布也显著增加（P<0.05）。此外，所有ZnT免疫反应检测到大多数淀粉样斑块和淀粉样血管病变的血管。ZnT 1和ZnT 4广泛表达于斑块的各个部位。ZnT 3、ZnT 5和ZnT 6在斑块周边部分的退化神经突中表达最显著，而ZnT 7存在于斑块的核心。淀粉样血管病变的血管表现出强烈的ZnT 3免疫反应。这些结果可能表明ZnTs在Aβ组合物的沉积和组织中的多种作用。
Pathological accumulation of β-amyloid peptide (Aβ) is an early and common feature of Alzheimer's disease (AD). An increased zinc concentration can initiate the deposition of Aβ. The present study aimed to study the expression and distribution patterns of six members of the zinc transporter (ZnT) family, ZnT1, ZnT3, ZnT4, ZnT5, ZnT6, and ZnT7, in the APPswe/PS1dE9 transgenic mouse brain. Our results demonstrated a statistically significant (P<0.05) increase of ZnT1, ZnT3, ZnT4, ZnT6, and ZnT7 in both hippocampus and neo-cortex using Western blot method and an abundant distribution of zinc ions in the plaques and amyloid angiopathic vessels using immersion autometallography. Furthermore, all ZnT immunoreactions were detected in most amyloid plaques and amyloid angiopathic vessels. ZnT1 and ZnT4 were extensively expressed in all parts of the plaques. ZnT3, ZnT5, and ZnT6 were expressed most prominently in the degenerating neurites in the peripheral part of the plaques, while ZnT7 was present in the core of the plaques. The amyloid angiopathic vessels showed a strong ZnT3 immunoreactivity. These results might suggest multiple roles of ZnTs in the deposition and organization of the Aβ composition.