Mechanisms of DHA-enriched phospholipids in improving cognitive deficits in aged SAMP8 mice with high-fat diet.

Recent studies have shown that a high-fat diet (HFD) is involved in both metabolic dysfunction and cognitive deficiency and that docosahexaenoic-acid-enriched phospholipids (DHA-PLs) have beneficial effects on obesity and cognitive impairment. However, there are only a few studies comparing differences between DHA-PC and DHA-PS in HFD-induced Alzheimer's disease (AD) models. After 8 weeks feeding with HFD, 10-month-old SAMP8 mice were fed with 1% (w/w) DHA-PC or 1% DHA-PS (biosynthesized from DHA-PC) for 8 weeks; we then tested the behavioral performances in the Barnes maze test and Morris maze test. The changes of the generation and accumulation of Aβ, oxidative stress, apoptosis, neuroinflammation and neurotrophic factors were also measured. The results indicated that both DHA-PC and DHA-PS significantly improved the metabolic disorders and cognitive deficits. Both DHA-PC and DHA-PS could ameliorate oxidative stress, and DHA-PS presented more notable benefits than DHA-PC on Aβ pathology, mitochondrial damage, neuroinflammation and neurotrophic factors; DHA-PS was for the first time found to increase the production of insoluble Aβ (less pathogenic) in this AD model. These data suggest that DHA-PLs can significantly improve cognitive deficiency, and the molecular mechanisms for this closely relate to the phospholipid polar groups.