Chronic administration of docosahexaenoic acid ameliorates the impairment of spatial cognition learning ability in amyloid β-infused rats
Chronic administration of docosahexaenoic acid ameliorates the impairment of spatial cognition learning ability in amyloid β-infused rats
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DOI：
10.1093/jn/135.3.549
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发表时间：
2005-03-01
影响因子：
4.2
通讯作者：
Shido, O
中科院分区：
文献类型：
--
作者：
Hashimoto, M;Tanabe, Y;Shido, O
我们研究了给予二十二碳六烯酸（DHA）（一种脑的主要（n-3）脂肪酸）是否改善阿尔茨海默病（AD）动物模型中的学习能力损伤，所述动物模型是向脑室中注入淀粉样β（Abeta）肽（1-40）的大鼠。将喂食鱼油缺乏饮食的近交系第3代雄性大鼠（20周龄）随机分为4组：载体组、Abeta肽注入组（Ap组）、DHA组和AP + DHA组。在大鼠体内植入一个装有AP肽或溶剂的微型渗透泵，并在八臂径向迷宫中测试它们的学习能力相关的参考和工作记忆。然后以300 mg/（kg.）d）（DHA和AP + DHA组）或单独的媒介物（媒介物和AP组），并再次测试学习能力。连续12周给予DHA可显著降低A β灌注大鼠的参考记忆和工作记忆错误次数的增加，并增加皮质-海马DHA水平和DHA/花生四烯酸的摩尔比，提示改善受损的空间认知学习能力。此外，DHA抑制了注入Abeta的大鼠大脑皮层和海马中脂质过氧化物和活性氧水平的增加，这表明DHA增加了抗氧化防御。因此，DHA是一种可能的治疗剂，用于改善由于阿尔茨海默病引起的学习缺陷。
We investigated whether administration of docosahexaenoic acid (DHA), a major (n-3) fatty acid of the brain, ameliorates the impairment of learning ability in an animal model of Alzheimer's disease (AD), rats infused with amyloid-beta (Abeta) peptide (1-40) into the cerebral ventricle. Inbred 3rd generation male rats (20 wk old) fed a fish oil-deficient diet were randomly divided into 4 groups: a vehicle group, an Abeta peptide-infused group (Ap group), a DHA group, and an AP + DHA group. A mini-osmotic pump filled with AP peptide or vehicle was implanted in the rats, and they were tested for learning ability-related reference and working memory in an 8-arm radial maze. The rats were then orally fed DHA dissolved in 5% gum Arabic solution at 300 mg/(kg (.) d) (DHA and AP + DHA groups) or vehicle alone (vehicle and AP groups) and tested again for learning ability. DHA administered for 12 wk significantly reduced the increase in the number of reference and working memory errors in the Abeta-infused rats, and increased both the cortico-hippocampal level of DHA and the molar ratio of DHA/arachidonic acid, suggesting an amelioration of the impaired spatial cognition learning ability. Furthermore, DHA suppressed the increases in the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and the hippocampus of Abeta-infused rats, suggesting that DHA increases antioxidative defenses. DHA is thus a possible therapeutic agent for ameliorating learning deficiencies due to Alzheimer's disease.