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-acidenriched 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 A beta, 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 A beta pathology, mitochondrial damage, neuroinflammation and neurotrophic factors; DHA-PS was for the first time found to increase the production of insoluble Ala (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. (C) 2018 Elsevier Inc. All rights reserved.