The essentiality of arachidonic acid in addition to docosahexaenoic acid for brain growth and function.

The essentiality of arachidonic acid (ARA) and docosahexaenoic acid (DHA) for growth and brain function using delta-6-desaturase knockout (D6D-KO) mice and a novel artificial rearing method was investigated. Newborn male wild type (WT) and homozygous D6D-KO pups were separated from their dams within 48h and fed artificial milk containing α-linolenic acid and linoleic acid (Cont), or supplemented with ARA, DHA or both (ARA+DHA). After weaning, each group was fed diets similar to artificial milk in fatty acid composition for 7 weeks. KO-Cont showed a lower body weight than WT-Cont. When ARA was added to the control diet, (KO-ARA and KO-ARA+DHA diets) the body weight gain was restored. The KO-DHA group was initially similar to the WT groups for the first 6 weeks, but afterwards their body weight was significantly lower. Brain weight in the 10 week old KO-ARA+DHA group was significantly higher within the KO dietary groups. Motor activity of the KO-ARA and KO-ARA+DHA groups was elevated relative to the KO-Cont group but the KO-ARA+DHA group exhibited similar activity to the WT-Cont group. In the motor coordination ability test, the KO-Cont group performed significantly worse compared with the WT-Cont group. KO-ARA mice showed decreased motor coordination in spite of their increased motor activity. The best performance was observed in only KO-ARA+DHA mice. These experiments demonstrated that supplementation with only ARA or only DHA was insufficient for optimal development. ARA was essential for normal growth within the lactation period. In conclusion, only the combination of preformed ARA and DHA was capable of improving the dysfunction caused by D6D deficiency.

Essentiality of arachidonic acid intake in murine early development.

We previously reported the importance of long-chain polyunsaturated fatty acid (LC-PUFA (>C20)) intake, including arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), for growth. This follow-up study focuses on ARA using a novel artificial rearing model during the lactation period in delta-6-desaturase knockout (D6D-KO) mice. Newborn D6D-KO male mouse pups were separated from dams within 48 hours and fed artificial milks containing 18-C essential fatty acids (EFAs) (16-17% LA, 3.8-4.1% ALA) with or without 1.2% ARA. After weaning, mice were maintained on similar diets: 15% LA, 2.3-2.4% ALA with or without 1.9% ARA. As a reference group, new born wild type (WT) male mouse pups were maintained by artificial milk and diet containing LA and ALA without ARA. Aspects of brain function were measured behaviorally (motor activity and rota-rod test) when mice were age 9 weeks. Body weight in the KO-Cont group was significantly lower (approximately 30%) than in the WT-Cont group, but this decrease was ameliorated by providing ARA in the KO-ARA group. The motor activity and coordination in the KO-Cont group decreased markedly compared to the WT-Cont group. The KO-ARA group had a tendency toward deteriorated motor coordination, although the motor activity was significantly enhanced compared to the KO-Cont group. In KO-ARA group brains, the level of ARA was increased and DHA decreased compared to WT-Cont. These results suggest that intake of LA and ALA only is insufficient to support healthy growth, and that ARA is also required, at least during the lactation period. These findings also suggested that continued intake of relatively high levels of ARA and without supplemental DHA during development led to an increased motor activity above that of WT animals. These studies indicate that both ARA dose and proper combination with DHA must be delineated to define optimal growth and behavioral function.