Differential effect of arachidonic acid and docosahexaenoic acid on age-related decreases in hippocampal neurogenesis

Hippocampal neurogenesis affects learning and memory. We evaluated in rats effects of ingestion of arachidonic acid (ARA) and/or docosahexaenoic acid (DHA) on age-related decreases in proliferating neural stem/progenitor cells (NSPCs) or newborn neurons (NNs). Rats were fed with ARA- and/or DHA-containing diet from 2 to 18 months old and then sacrificed 1 day or 4 weeks after 5-bromo-2-deoxyuridine (BrdU) injections at 2, 6 and 18 months. The numbers of NSPCs (SOX2+/BrdU+) and NNs (NeuN+/BrdU+) were determined immunohistochemically. The number of BrdU+ cells 1 day after BrdU injections decreased with age, but increased 65% after ARA ingestion compared to the control at 18 months. The SOX2+/BrdU+ cell ratio was unchanged by aging or ingestion of ARA or DHA. The number of NeuN+/BrdU+ cells 4 weeks after BrdU injections decreased with age, but increased 34% (yet not statistically significant) after DHA ingestion compared to the control at 18 months. These results indicate that ARA ingestion can ameliorate the age-related decrease in the number of NSPCs in rats. The functions of ARA and DHA in hippocampal neurogenesis appear to be different in aged rats; ARA may maintain an NSPC pool, whereas DHA may support NN production and/or survival.