Protective effects of prescription n-3 fatty acids against impairment of spatial cognitive learning ability in amyloid β-infused rats

Deposition of amyloid beta peptide (A beta) into the brain causes cognitive impairment. We investigated whether prescription pre-administration of n-3 fatty acids improves cognitive learning ability in young rats and whether it protects against learning ability impairments in an animal model of Alzheimer's disease that was prepared by infusion of A beta(1-40) into the cerebral ventricles of rats. Pre-administration of TAK-085 ( highly purified and concentrated n-3 fatty acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of reference memory errors in an 8-arm radial maze, suggesting that long-term administration of TAK-085 improves cognitive leaning ability in rats. After pre-administration, the control group was divided into the vehicle and A beta-infused groups, whereas the TAK-085 pre-administration group was divided into the TAK-085 and TAK-085 + A beta groups (TAK-085-pre-administered A beta-infused rats). A beta(1-40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Pre-administration of TAK-085 to the A beta-infused rats significantly suppressed the number of reference and working memory errors and decreased the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus of A beta-infused rats, suggesting that TAK-085 increases antioxidative defenses. The present study suggests that long-term administration of TAK-085 is a possible therapeutic agent for protecting against Alzheimer's disease-induced learning deficiencies.