Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, Japan.
Food Funct. 2011 Jul;2(7):386-94. doi: 10.1039/c1fo00002k. Epub 2011 Jul 8.
Deposition of amyloid β peptide (Aβ) into the brain causes cognitive impairment. We investigated whether prescription pre-administration of n-3 fatty acids improves cognitive learning ability in young rats and whether it protects against learning ability impairments in an animal model of Alzheimer's disease that was prepared by infusion of Aβ(1-40) into the cerebral ventricles of rats. Pre-administration of TAK-085 (highly purified and concentrated n-3 fatty acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of reference memory errors in an 8-arm radial maze, suggesting that long-term administration of TAK-085 improves cognitive leaning ability in rats. After pre-administration, the control group was divided into the vehicle and Aβ-infused groups, whereas the TAK-085 pre-administration group was divided into the TAK-085 and TAK-085 + Aβ groups (TAK-085-pre-administered Aβ-infused rats). Aβ(1-40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Pre-administration of TAK-085 to the Aβ-infused rats significantly suppressed the number of reference and working memory errors and decreased the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus of Aβ-infused rats, suggesting that TAK-085 increases antioxidative defenses. The present study suggests that long-term administration of TAK-085 is a possible therapeutic agent for protecting against Alzheimer's disease-induced learning deficiencies.
淀粉样β肽（Aβ）在脑内沉积导致认知功能障碍。我们研究了 n-3 脂肪酸是否能改善年轻大鼠的认知学习能力，以及是否能预防通过向大鼠脑室内输注 Aβ（1-40）制备的阿尔茨海默病动物模型中的学习能力障碍。TAK-085（高纯度和浓缩的 n-3 脂肪酸，含有二十碳五烯酸乙酯和二十二碳六烯酸乙酯）在 12 周内以 300mg/kg/d 的剂量进行预给药，显著减少了在 8 臂放射状迷宫中的参考记忆错误数量，表明长期给予 TAK-085 可改善大鼠的认知学习能力。预给药后，对照组分为载体组和 Aβ 输注组，而 TAK-085 预给药组分为 TAK-085 组和 TAK-085+Aβ 组（TAK-085 预给药+Aβ 输注大鼠）。通过微量渗透泵将 Aβ（1-40）或载体输注到脑室内。TAK-085 预给药显著抑制了 Aβ 输注大鼠的参考和工作记忆错误数量，并降低了 Aβ 输注大鼠大脑皮质和海马中的脂质过氧化物和活性氧的水平，表明 TAK-085 增加了抗氧化防御能力。本研究表明，长期给予 TAK-085 可能是一种预防阿尔茨海默病引起的学习能力下降的治疗药物。
