Effects of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on brain development using artificial rearing of delta-6-desaturase knockout mice

This study focused on the effect of polyunsaturated fatty acids (PUFAs) during the lactation period of delta-6-desaturase knockout (D6D-KO) mice using an artificial rearing method. Newborn pups of D6D-KO male mice were separated from their dams within 48 h and were fed artificial milk. Six formulations of milk were used: Control (Cont) milk (3.9% α-linolenic acid and 18% linoleic acid), + 1.3% arachidonic acid (ARA), + 1.2% docosahexaenoic acid (DHA), + 1.3% eicosapentaenoic acid (EPA), + 1.1% ARA + 1.3% DHA, and + 1.3% ARA + 1.3% EPA. After weaning, the mice were fed pelleted diets containing a similar fatty acid composition as during lactation. Brain function was measured using a behavioral approach including motor activity and the Morris water maze test at 9 weeks of age. The body weight of the KO Cont group was significantly lower than that of the wild-type (WT) group; however, the ARA, ARA+DHA and ARA+EPA groups were similar to the WT group. In the Morris water maze test, the DHA and ARA+DHA groups demonstrated learning and memory performance similar to the WT group; however, the Cont group exhibited quite poor learning performance. Interestingly, the ARA, EPA and ARA+EPA groups showed intermediate performance between the Cont and WT groups. These results suggested that the 18-C essential fatty acids linoleic and α-linolenic were not sufficient to support optimal growth and neural performance. ARA was the most critical long-chain PUFA for supporting body growth. In addition, DHA was clearly essential for brain function. Taken together, these results indicate that the combination of DHA and ARA is essential for optimal growth and development in early life.