Oral Administration of Synthetic Retinoid Am80 (Tamibarotene) Decreases Brain β-Amyloid Peptides in APP23 Mice
Oral Administration of Synthetic Retinoid Am80 (Tamibarotene) Decreases Brain β-Amyloid Peptides in APP23 Mice
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DOI：
10.1248/bpb.32.1307
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发表时间：
2009-07-01
影响因子：
2
通讯作者：
Nakayama, Hitoshi
中科院分区：
文献类型：
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作者：
Kawahara, Kohichi;Nishi, Kentaro;Nakayama, Hitoshi
本研究的目的是调查合成类视黄醇 Am80（他米巴罗汀）是否对淀粉样前体蛋白 (APP)23 小鼠（阿尔茨海默病模型）表现出任何改善作用。 Am80以0（对照）或0.5mg/kg/d的剂量口服给20周（5个月）大的APP23小鼠饲料，持续14周。 Am80治疗显着降低了大脑中不溶性Aβ水平，特别是Aβ(42)，但对可溶性Aβ水平没有明显影响。结果表明，口服Am80可能具有减少不溶性且可能寡聚或原纤维形式的细胞外Aβ(42)的效力，这与阿尔茨海默氏病的病因和/或进展有关。 Morris水迷宫分析表明Am80治疗对APP23小鼠的空间学习和记忆没有显着影响。缺乏显着性的主要原因似乎是基于较大的偏差，并且处理组和未处理组中的一些小鼠既不会游泳也不会努力到达平台。
The purpose of this study is to investigate whether a synthetic retinoid Am80 (tamibarotene) exhibits any improving effects on amyloid precursor protein (APP)23 mice, a model of Alzheimer's disease. Am80 was orally administered in feed to 20-week (5-month)-old APP23 mice at a dose of 0 (control) or 0.5mg/kg/d for 14 weeks. The Am80 treatment reduced significantly the insoluble A beta levels in brain, in particular A beta(42), while it gave no apparent effects on the soluble A beta levels. The results suggest that oral administration of Am80 may have potency to reduce the extracellular A beta(42) of insoluble and possibly oligomeric or protofibril forms, which are related to the cause and/or progression of Alzheimer's disease. The Am80 treatment showed no significant effect on spatial learning and memory of APP23 mice by Morris water maze analysis. The main reason for the absence of significance seems based on the large deviation and some mice both in the treated and the non-treated groups would neither swim nor make efforts to reach the platform.