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The pathogenic mechanism of dementia is still unknown, and the fundamental treatment remains to be established. Thus, there is growing interest in preventing dementia through diet. One of the functional ingredients attracting attention is docosahexaenoic acid. We conducted a 12-month, randomized, doubleblind, placebo-controlled clinical trial in healthy elderly Japanese individuals with a Mini-Mental State Examination score of 28 or higher at baseline using a docosahexaenoic acid-enriched milk beverage containing 297 mg docosahexaenoic acid and 137 mg eicosapentaenoic acid. Consumption of a docosahexaenoic acid-enriched milk beverage increased the fatty acid levels of docosahexaenoic acid and eicosapentaenoic acid in erythrocyte membranes, which was the primary outcome of this study. Moreover, intake of this beverage prevented age-related cognitive decline and decreased serum bone resorption marker levels. Our data demonstrate that, even at a low dose, long-term daily intake of docosahexaenoic acid prevents dementia and may show beneficial effect on bone health. [ABSTRACT FROM AUTHOR]

Background: Arachidonic acid (AA, C20:4, ω-6) is a ω-6 polyunsaturated fatty acid (PUFA) and plays diverse roles in cell signaling. Numerous reports on the effects of ω-3 PUFAs, such as docosahexaenoic acid (DHA, C22:6, ω-3) and eicosapentaenoic acid (EPA, C20:5, ω-3) on learning and memory impairments of rats are available, however, the role of AA on brain cognition is largely unknown. Objective: In this study, our aim was to investigate the effect of oral administration of AA on spatial memory- related learning ability in aged (100 weeks) male rats. Design: One group was per orally administered 240 mg/kg per day AA oil and the other group was administered the similar volume of control oil. Five weeks after the start of the administration, rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Also, the time required to complete the task was recorded. The levels of lipid peroxide (LPO) and reactive oxygen species (ROS) were measured, as an indicator oxidative stress in the plasma and brain corticohippocampal brain tissues. Results: The scores of RMEs and WMEs, which are analogous to long-term and short-term memory, respectively, were not affected, however, the trial time was shorter in the AA-administered rats than that of the controls. AA also significantly increased the degree of oxidative stress both in the plasma and corticohippocampal brain tissues. Conclusions: Our results suggest that though AA deposition in the corticohippocampal tissues of senescent rats caused a faster performance activity, which is reminiscent to hyperactive behavior of animals, the spatial learning ability-related memory of the rats, however, was not improved. [ABSTRACT FROM AUTHOR]

Polyunsaturated fatty acids (PUFAs) can induce neurogenesis and recovery from brain diseases. However, the exact mechanisms of the bene..cial effects of PUFAs have not been conclusively described. We recently reported that docosahexaenoic acid (DHA) induced neuronal differentiation by decreasing Hes1 expression and increasing p27kip1 expression, which causes cell cycle arrest in neural stem cells (NSCs). In the present study, we examined the effect of eicosapentaenoic acid (EPA) and arachidonic acid (AA) on differentiation, expression of basic helix-loop-helix transcription factors (Hes1, Hes6, and NeuroD), and the cell cycle of cultured NSCs. EPA also increased mRNA levels of Hes1, an inhibitor of neuronal differentiation, Hes6, an inhibitor of Hes1, NeuroD, and Map2 mRNA and Tuj-1-positive cells (a neuronal marker), indicating that EPA induced neuronal differentiation. EPA increased the mRNA levels of p21cip1 and p27kip1, a cyclin-dependent kinase inhibitor, which indicated that EPA induced cell cycle arrest. Treatment with AA decreased Hes1 mRNA but did not affect NeuroD and Map2 mRNA levels. Furthermore, AA did not affect the number of Tuj-1-positive cells or cell cycle progression. These results indicated that EPA could be involved in neuronal differentiation by mechanisms alternative to those of DHA, whereas AA did not affect neuronal differentiation in NSCs. [ABSTRACT FROM AUTHOR]

We have previously reported that dietary docosahexaenoic acid (DHA) improves and/or protects against impairment of cognition ability in amyloid beta1-40 (Aβ1-40)-infused Alzheimer’s disease (AD)-model rats. Here, after the administration of DHA to AD model rats for 12 weeks, the levels of Aβ1-40, cholesterol and the composition of fatty acids were investigated in the Triton X100-insoluble membrane fractions of their cerebral cortex. The effects of DHA on the in vitro formation and kinetics of fibrillation of Aβ1-40 were also investigated by thioflavin T fluorescence spectroscopy, transmission electron microscopy and fluorescence microscopy. Dietary DHA significantly decreased the levels of Aβ1-40, cholesterol and saturated fatty acids in the detergent insoluble membrane fractions of AD rats. The formation of Aβ fibrils was also attenuated by their incubation with DHA, as demonstrated by the decreased intensity of thioflavin T-derived fluorescence and by electron micrography. DHA treatment also decreased the intensity of thioflavin fluorescence in preformed-fibril Aβ peptides, demonstrating the anti-amyloidogenic effects of DHA. We then investigated the effects of DHA on the levels of oligomeric amyloid that is generated during its in vitro transformation from monomers to fibrils, by an anti-oligomer-specific antibody and non-reducing Tris-Glycine gradient (4–20%) gel electrophoresis. DHA concentration-dependently reduced the levels of oligomeric amyloid species, suggesting that dietary DHA-induced suppression of in vivo Aβ1-40 aggregation occurs through the inhibitory effect of DHA on oligomeric amyloid species. [ABSTRACT FROM AUTHOR]