Chronic Administration of Docosahexaenoic Acid Ameliorates the Impairment of Spatial Cognition Learning Ability in Amyloid β–Infused Rats

Abstract

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-β (Aβ) 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 Aβ peptide-infused group (Aβ group), a DHA group, and an Aβ + DHA group. A mini-osmotic pump filled with Aβ 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 Aβ + DHA groups) or vehicle alone (vehicle and Aβ 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 Aβ-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 Aβ-infused rats, suggesting that DHA increases antioxidative defenses. DHA is thus a possible therapeutic agent for ameliorating learning deficiencies due to Alzheimer's disease.