Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid β-infused rats relates to the decreases of amyloid β and cholesterol levels in detergent-insoluble membrane fractions
Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid β-infused rats relates to the decreases of amyloid β and cholesterol levels in detergent-insoluble membrane fractions
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DOI：
10.1016/j.bbalip.2005.11.011
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发表时间：
2005-12-30
影响因子：
4.8
通讯作者：
Shido, O
中科院分区：
文献类型：
--
作者：
Hashimoto, M;Hossain, S;Shido, O
我们研究了饮食给药二十二碳六烯酸（DHA; C22:6n-3）对大脑皮层非离子清洁剂Triton 100x不溶性膜部分（DIFs）中淀粉样蛋白β (A β)肽（1-40）和胆固醇水平的影响，以及对阿尔茨海默病（AD）动物模型大鼠脑室注入β肽（1-40）的学习相关记忆的影响。与载药大鼠相比，注射增加了dif中A β肽和胆固醇的水平，同时显著增加了参考记忆误差（通过八臂径向迷宫任务测量）。相反，给ad模型大鼠饮食中添加DHA降低了DlFs中A- β肽和胆固醇的水平，在DHA模型大鼠中下降更为明显。回归分析显示，a β肽与胆固醇、棕榈酸、硬脂酸、参考记忆错误数与胆固醇、棕榈酸、硬脂酸、油酸均呈显著正相关；此外，DHA与棕榈酸和硬脂酸的摩尔比与参考记忆错误数呈显著负相关。这些结果表明，DHA诱导的ad模型大鼠记忆缺陷保护与胆固醇、棕榈酸或硬脂酸与DIFs中A β肽的相互作用有关，其中DHA改善了这些相互作用。(c) 2005 Elsevier B.V.版权所有
We investigated the effects of dietary administration of docosahexaenoic acid (DHA; C22:6n-3) on the levels of amyloid beta (A beta) peptide (1-40) and cholesterol in the nonionic detergent Triton 100x-insoluble membrane fractions (DIFs) of the cerebral cortex and, also, on learning-related memory in an animal model of Alzheimer's disease (AD) rats infused with A beta peptide (1-40) into the cerebral ventricle. The infusion increased the levels of A beta peptide and cholesterol in the DIFs concurrently with a significant increase in reference memory errors (measured by eight-arm radial-maze tasks) compared with those of vehicle rats. Conversely, the dietary administration of DHA to AD-model rats decreased the levels of A beta peptide and cholesterol in the DlFs, with the decrease being more prominent in the DHA-administered rats. Regression analysis revealed a significant positive correlation between A beta peptide and each of cholesterol, palmitic acid and stearic acid, and between the number of reference memory errors and each of cholesterol, palmitic, stearic and oleic acid; moreover, a significant negative correlation was observed between the number of reference memory errors and the molar ratio of DHA to palmitic plus stearic acid. These results suggest that DHA-induced protection of memory deficits in AD-model rats is related to the interactions of cholesterol, palmitic acid or stearic acid with A beta peptides in DIFs where DHA ameliorates these interactions. (c) 2005 Elsevier B.V. All rights reserved.