The protective effect of dietary eicosapentaenoic acid against impairment of spatial cognition learning ability in rats infused with amyloid β(1-40)

Background: Amyloid beta (A beta) peptide (1-40) can cause cognitive impairment. Experimental design: We investigated whether dietary preadministration of eicosapentaenoic acid (EPA) is conducive to cognition learning ability and whether it protects against the impairment of learning ability in rats infused with A beta peptide (1-40) into the cerebral ventricle. Results: Dietary EPA administered to rats for 12 weeks before the infusion of A beta into the rat brain significantly decreased the number of reference memory errors (RMEs) and working memory errors (WMEs), suggesting that chronic administration of EPA improves cognition learning ability in rats. EPA preadministered to the A beta-infused rats significantly reduced the increase in the number of RMEs and WMEs, with concurrent proportional increases in the levels of corticohippocampal EPA and docosahexaenoic acid (DHA) and in the DHA/arachidonic acid molar ratio. Decrease in oxidative stress in these tissues was evaluated by determining the reactive oxygen species and lipid peroxide levels. cDNA microarray analysis revealed that altered genes included those that control synaptic signal transduction, cell communication, membrane-related vesicular transport functions, and enzymes and several other proteins. Conclusion: The present study suggests that EPA, by acting as a precursor for DHA, ameliorates learning deficits associated with Alzheimer's disease and that these effects are modulated by the expression of proteins involved in neuronal plasticity. (C) 2009 Elsevier Inc. All rights reserved.