The role of essential fatty acids in brain development

Abstract

Arachidonic acid （ARA） and docosahexaenoic acid （DHA） are the principal n-6 and n-3 polyunsaturated fatty acids （PUFAs） in the brain, respectively, and essential for proper brain development. Previous in vitro studies have revealed that ARA induces astrocytic differentiation of neural stem cells （NSCs）， and that DHA induces neuronal differentiation of NSCs. Thus, n-6 and n-3 PUFAs have different roles in brain development. Regarding the evaluation of in vivo roles of these PUFAs, the balance of n-6/n-3 PUFAs is considered to be important because these PUFAs compete each other in their synthesis, metabolism, and transport. Indeed, we have reported neurodevelopmental consequences of maternal consumption of an n-6-rich/n-3-poor diet in mice. We found that epoxy metabolites of ARA and DHA oppositely regulated the neurogenic-to-gliogenic fate transition of NSCs, and consequently they affected brain development. These findings are scientifically and socially important, because intake of seed oils, which are abundant in n-6 PUFAs, and that of fishes, which are abundant in n-3 PUFAs, have recently been increased and decreased, respectively, in many countries. In another study from our collaborators, a mouse model for schizophrenia has been proposed based on phenotypes of offspring derived from pregnant mice fed a PUFA-deficient diet. In the present review, we summarize the functions of dietary n-6 and n-3 PUFAs in brain development.