Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats
Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats
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DOI：
10.1046/j.1471-4159.2002.00905.x
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发表时间：
2002-06-01
影响因子：
4.7
通讯作者：
Shido, O
中科院分区：
文献类型：
--
作者：
Hashimoto, M;Hossain, S;Shido, O
二十二碳六烯酸（C22:6，n - 3）是大脑中一种主要的n - 3脂肪酸，已被认为与记忆相关功能的恢复和增强有关。由于阿尔茨海默病会损害记忆，并且向大鼠脑室注入β - 淀粉样蛋白（Aβ）肽（1 - 40）会降低学习能力，我们研究了在Aβ肽诱导的阿尔茨海默病模型大鼠中，预先给予膳食二十二碳六烯酸对回避学习能力的影响。在给喂食二十二碳六烯酸的大鼠和对照大鼠植入装满Aβ肽或赋形剂的微型渗透泵后，将它们置于穿梭回避系统装置中进行主动回避任务。预先给予二十二碳六烯酸对阿尔茨海默病模型大鼠回避学习能力的下降具有非常有益的影响，这与皮质 - 海马二十二碳六烯酸/花生四烯酸摩尔比的增加以及神经元凋亡产物的减少有关。预先给予二十二碳六烯酸还增加了皮质 - 海马还原型谷胱甘肽水平和谷胱甘肽还原酶活性，并抑制了阿尔茨海默病模型大鼠大脑皮质和海马中脂质过氧化物和活性氧水平的升高，表明抗氧化防御能力增强。因此，二十二碳六烯酸可能是一种预防阿尔茨海默病学习缺陷的预防手段。
Docosahexaenoic acid (C22:6, n-3), a major n-3 fatty acid of the brain, has been implicated in restoration and enhancement of memory-related functions. Because Alzheimer's disease impairs memory, and infusion of amyloid-beta (Abeta) peptide (1-40) into the rat cerebral ventricle reduces learning ability, we investigated the effect of dietary pre-administration of docosahexaenoic acid on avoidance learning ability in Abeta peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Abeta peptide or vehicle was implanted in docosahexaenoic acid-fed and control rats, they were subjected to an active avoidance task in a shuttle avoidance system apparatus. Pre-administration of docosahexaenoic acid had a profoundly beneficial effect on the decline in avoidance learning ability in the Alzheimer's disease model rats, associated with an increase in the cortico-hippocampal docosahexaenoic acid/arachidonic acid molar ratio, and a decrease in neuronal apoptotic products. Docosahexaenoic acid pre-administration furthermore increased cortico-hippocampal reduced glutathione levels and glutathione reductase activity, and suppressed the increase in lipid peroxide and reactive oxygen species levels in the cerebral cortex and hippocampus of the Alzheimer's disease model rats, suggesting an increase in antioxidative defence. Docosahexaenoic acid is thus a possible prophylactic means for preventing the learning deficiencies of Alzheimer's disease.