Green tea epigallocatechin-3-gallate (EGCG) reduces β-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice
Green tea epigallocatechin-3-gallate (EGCG) reduces β-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice
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DOI：
10.1016/j.brainres.2008.02.107
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发表时间：
2008-06-12
期刊：
影响因子：
2.9
通讯作者：
Tan, Jun
中科院分区：
文献类型：
--
作者：
Rezai-Zadeh, Kavon;Arendash, Gary W.;Tan, Jun
我们先前报道了腹膜内（i. p.）注射（20 mg/kg）（-）-表没食子儿茶素-3-没食子酸酯（EGCG）（绿色茶的主要多酚成分）通过促进“瑞典”突变淀粉样前体蛋白过表达（APPsw，Tg）小鼠中非淀粉样蛋白生成α-分泌酶蛋白水解途径降低β-淀粉样蛋白（A β）水平和斑块。在这里，我们发现在饮用水中口服给予EGCG（50 mg/kg）类似地减少了这些小鼠中的A β沉积。对8个月龄的队列进行6个月治疗后，冠状切片的免疫组织化学分析显示，扣带皮层、海马和内嗅皮层中的斑块负荷分别减少了54%、43%和51%。扣带皮层、海马和内嗅皮层中的刚果红斑块负荷也分别降低了53%、53%和58%。治疗Tg小鼠的脑匀浆的ELISA显示A β（1-40）和（1-42）可溶性和不溶性形式的一致减少。在本研究中，我们还研究了EGCG给药对Tg小鼠中tau病理学和认知的影响。发现腹膜内和口服治疗的Tg动物都具有调制的tau谱，具有显著抑制的肌氨酰可溶性磷酸化tau亚型。放射状神经网络水迷宫（RAWM）工作记忆测试表明，腹腔注射和口服给予EGCG对Tg小鼠都有认知益处，尽管腹腔注射-口服给予EGCG对Tg小鼠的认知益处是显著的。治疗的动物显示出更明显的益处，因为在测试时它们的Tg控制受到更大的损害。总而言之，这些数据进一步证实了EGCG膳食补充剂作为阿尔茨海默病潜在安全有效的预防方法的概念。(C)2008由爱思唯尔公司出版
We previously reported that intraperitoneal (i.p.) injection (20 mg/kg) of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, decreased beta-amyloid (A beta) levels and plaques via promotion of the non-amyloidogenic alpha-secretase proteolytic pathway in "Swedish" mutant amyloid precursor protein overexpressing (APPsw, Tg) mice. Here, we find that EGCG administered orally in drinking water (50 mg/kg) similarly reduces A beta deposition in these mice. Following a six month treatment of an 8 month old cohort, immunohistochemical analysis of coronal sections reveals that plaque burdens were reduced in the cingulate cortex, hippocampus, and entorhinal cortex by 54%, 43%, and 51%, respectively. Congo red plaque burdens were decreased in the cingulate cortex, hippocampus, and entorhinal cortex by 53%, 53%, and 58%, respectively as well. ELISA of brain homogenates of the treatment Tg mice revealed consistent reductions in both A beta(1-40) and (1-42) soluble and insoluble forms. In the present study we also investigated the effect EGCG administration had on tau pathology and cognition in Tg mice. Both i.p. and orally-treated Tg animals were found to have modulated tau profiles, with markedly suppressed sarkosyl-soluble phosphorylated tau isoforms. Radial ann water maze (RAWM) testing for working memory indicated that EGCG provided cognitive benefit to Tg mice with both i.p. and oral administration, although i.p.-treated animals showed a more pronounced benefit because of the greater impairment of their Tg controls at the time of testing. Taken together, these data further the notion of EGCG dietary supplementation as a potentially safe and effective prophylaxis for Alzheimer's disease. (C) 2008 Published by Elsevier B.V.