Maternal Fish Oil Supplementation: The Prodrom of Synaptic Protection in Alzheimer's Disease

Prospective longevity is overshadowed by the high prevalence of mental decline in aging. Hence, nutritional indications are a crucial element in today's observed aging of the population. There is now growing epidemiological evidence suggesting that reduced levels of docosahexaenoic acid [DHA, 22:6, (n-3)] may be indicative of an increased risk of Alzheimer's disease (AD). On the other hand, the Mediterranean diet includes high intake of fatty fish and has been associated with lower AD risk; fish is the major food source of DHA. Recently three new families of DHA-derived mediators - termed D series resolvins (RvDs, 17S epimers), protectins (NPDs, 17S epimers) and maresins - have been uncovered; these new bioactive lipids confer potent cellular protection. In the presence of aspirin (ASA), equipotent ASA-triggered 17R epimers (ASA-RvDs and ASA-NPDs) were produced in vivo. However, while enzymatic oxidation dramatically reduced the bioactivity of 17S epimers RvDs and NPDs, enzymatic conversion of ASA-17R epimers was sharply reduced. Specifically, as ASA-DHA-derived lipids have cellular protective actions, the resistance to rapid inactivation may contribute to the beneficial actions of omega-3 (n-3) fish oils and ASA in humans and offers new insights into the prevention of neurodegenerative diseases.