Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse.
Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse.
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DOI：
10.1016/j.bbrc.2006.09.083
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发表时间：
2006-11
影响因子：
3.1
通讯作者：
Y. Nishida;T. Yokota;Tsubura Takahashi;T. Uchihara;K. Jishage;H. Mizusawa
中科院分区：
文献类型：
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作者：
Y. Nishida;T. Yokota;Tsubura Takahashi;T. Uchihara;K. Jishage;H. Mizusawa
氧化损伤增加是阿尔茨海默病（AD）的一个突出和早期特征。然而，它是否是AD病理学的主要原因或仅仅是下游后果仍是未知的。我们先前产生了α-生育酚转移蛋白敲除（Ttpa−/−）小鼠，其中通过完全耗尽α-生育酚（α-Toc）显著增加了脑中的脂质过氧化。在这里，我们将AD转基因（APPsw）模型小鼠（Tg 2576）与Ttpa−/−小鼠杂交。由此产生的双突变（Ttpa−/−APPsw）小鼠在Morris水迷宫、新物体识别和情境恐惧条件反射测试中表现出更早和更严重的认知功能障碍。通过免疫组织化学分析，他们还显示大脑中淀粉样β肽（Aβ）沉积增加，补充α-Toc后有所改善。在这份报告中，我们提供了明确的证据表明，由于α-Toc消耗慢性脂质过氧化增强AD小鼠模型的表型。
Increased oxidative damage is a prominent and early feature in Alzheimer disease (AD). However, whether it is a primary cause or merely a downstream consequence in AD pathology is still unknown. We previously generated α-tocopherol transfer protein knockout (Ttpa−/−) mice, in which lipid peroxidation in the brain was significantly increased by complete depletion of α-tocopherol (α-Toc). Here we crossed AD transgenic (APPsw) model mice (Tg2576) with Ttpa−/−mice. The resulting double-mutant (Ttpa−/−APPsw) mice showed earlier and more severe cognitive dysfunction in the Morris water maze, novel-object recognition, and contextual fear conditioning tests. They also showed increased amyloid β-peptide (Aβ) deposits in the brain by immunohistochemical analysis, which was ameliorated with α-Toc supplementation. In this report we provide clear evidence indicating that chronic lipid peroxidation due to α-Toc depletion enhances AD phenotype in a mouse model.