Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids.

Advanced age is associated with reduced brain levels of long-chain polyunsaturated fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA). Memory impairment is also a common phenomenon in this age. Two-year-old, essential fatty acid-sufficient rats were fed with fish oil (11% DHA) for 1 month, and fatty acid as well as molecular composition of the major phospholipids, phosphatidylcholine and phosphatidylethanolamine (PE), was compared with that of 2-month-old rats on the same diet. DHA but not AA was significantly reduced in brains of old rats but was restored to the level of young rats when they received rat chow fortified with fish oil. This effect was pronounced with diacyl 18:0/22:6 PE species, whereas levels of 18:1/22:6 and 16:0/22:6 remained unchanged in all of the three PE subclasses. Fish oil reduced the AA in the old rat brains, diacyl and alkenylacyl 18:0/20:4 PE being most affected. Phosphatidylcholines gave less pronounced response. Six genes were up-regulated, whereas no significant changes were observed in brains of old rats receiving fish oil for 1 month. None of them except synuclein in young rat brains could be related to mental functions. Old rats on the fish-oil diet did not perform better in Morris water maze test than the control ones. A 10% increase in levels of diacyl 18:0/22:6 PE in young rat brains resulted in a significant improvement of learning capacity. The results are interpreted in terms of the roles of different phospholipid molecular species in cognitive functions coupled with differential responsiveness of the genetic machinery of neurons to n-3 polyunsaturated fatty acids.