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‐β (Aβ) 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 Aβ peptide‐produced Alzheimer's disease model rats. After a mini‐osmotic pump filled with Aβ 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.

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.

Docosahexaenoic acid (DHA, C22:6, ω-3) is a highly polyunsaturated omega-3 fatty acid. It is concentrated in neuronal brain membranes, for which reason it is also referred to as a “brain food”. DHA is essential for brain development and function. It plays an important role in improving antioxidant and cognitive activities of the brain. DHA deficiency occurs during aging and dementia, impairs memory and learning, and promotes age-related neurodegenerative diseases, including Alzheimer’s disease (AD). For about two decades, we have reported that oral administration of DHA increases spatial memory acquisition, stimulates neurogenesis, and protects against and reverses memory impairment in amyloid β peptide-infused AD rat models by decreasing amyloidogenesis and protects against age-related cognitive decline in the elderly. These results demonstrate a robust link between DHA and cognitive health. Rodents that were fed a diet low in ω-3 polyunsaturated fatty acids, particularly those that were DHA-deficient, frequently suffered from anxiety, depression and memory impairment. Although the exact mechanisms of action of DHA in brain functions are still elusive, a host of mechanisms have been proposed. For example, DHA, which inherently has a characteristic three-dimensional structure, increases membrane fluidity, strengthens antioxidant activity and enhances the expression of several proteins that act as substrates for improving memory functions. It reduces the brain amyloid burden and inhibits in vitro fibrillation and amyloid-induced neurotoxicity in cell-culture model. In this review, we discuss how DHA acts as a molecule with diverse functions.

Green tea catechins confer potent biological properties including antioxidation and free-radical scavenging. We investigated the effect of long-term oral administration of green tea catechins (Polyphenon^R E, PE: EGCG 63%; EC 11%; EGC 6%; ECG 6%) mixed with water on the spatial cognition learning ability of young rats. The learning ability of rats administered PE (0%, 0.1%, 0.5%) for 26 wk was assessed in the partially baited 8-arm radial maze. Relative to controls, those administered PE had improved reference and working memory–related learning ability. They also had lower plasma concentrations of lipid peroxides and greater plasma ferric-reducing antioxidation power than controls. Furthermore, rats administered PE had lower hippocampus reactive oxygen species concentrations than controls. We suggest that this improvement in spatial cognitive learning ability is due to the antioxidative activity of green tea catechins.