An extraordinary degree of structural specificity is required in neural phospholipids for optimal brain function: n‐6 docosapentaenoic acid substitution for docosahexaenoic acid leads to a loss in spatial task performance

Abstract

This study was conducted to determine whether provision of preformed dietary docosapentaenoic acid (DPAn-6) can replace docosahexaenoic acid (DHA) for brain function as assessed by spatial task performance. A newly modified artificial rearing method was employed to generate n-3 fatty aciddeficient rats. Newborn pups were separated from their mothers at 2 days of age and given artificial rat milk containing linoleic acid (LA), or LA supplemented with 1% DHA (DHA), 1% DPAn-6 (DPA) or 1% DHA plus 0.4% DPAn-6 (DHA/DPA). The animals were then weaned onto similar pelleted diets. At adulthood, behavioural tasks were administered and then the brains were collected for fatty acid analysis. The LA and DPA groups showed a lower (63-65%) brain DHA than the damreared, DHA and DHA/DPA groups and this loss was largely compensated for by an increase in brain DPAn-6. The brain fatty acid composition in the DPA group was the same as that in the LA group at adulthood. In the Morris water maze, the LA and DPA groups exhibited a longer escape latency than the damreared and DHA groups and had a defect in spatial retention. In conclusion, DPAn-6 could not replace DHA for brain function, indicating a highly specific structural requirement for DHA.

Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats

“…During times of n-3 PUFA deprivation, it is apparent that the accretion of AA from LA is increased and AA is also further metabolized to produce 22:5n-6 (DPAn-6), which accumulates in tissues so as to reciprocally replace lost DHA (57)(58)(59)(60). Of all tissues examined, only kidney and brain were found to be changed in LA content, with an increase of 1.5-and 1.3-fold, respectively, in the d5-LNA 1 DHA compared with d5-LNA diet group.…”

Artificial rearing with docosahexaenoic acid and n-6 docosapentaenoic acid alters rat tissue fatty acid composition

“…The study design and experimental diets have been described in detail previously (13). In brief, pregnant, Long-Evans dams at day 3 of gestation were purchased from Charles River (Portage, MI) and maintained with ad libitum water at a controlled temperature (23 6 1jC) and a 12 h light/dark cycle.…”

“…The experimental milks varied in specific fatty acid content but were based on fat from hydrogenated coconut oil (Dyets, Bethlehem, PA), mediumchain triglycerides (Mead Johnson Nutritionals, Evansville, IN), and oleic and linoleic ethyl esters with or without DPAn-6 and/or docosahexaenoic ethyl esters added (Nu-Chek Prep, Elysian, MN). Details of the diet preparations are presented elsewhere (13). The four AR groups were fed an 18:2n-6-based diet (AR-LA), an 18:2n-6-based diet with 1% of total fatty acids as 22:5n-6 (AR-DPAn-6), an 18:2n-6-based diet with 1% of total fatty acids as 22:6n-3 (AR-DHA), and an 18:2n-6-based diet with 1% of total fatty acids as 22:6n-3 and 0.4% of total fatty acids as 22:5n-6 diet (AR-DHA1DPAn-6) ( Table 1).…”

“…Therefore, n-3 fatty acid deficiency studies using 18:2n-6-based control diets have the potential to increase the content of 20:4n-6, which has significant bioactive properties. Given that the reciprocal replacement of 22:6n-3 with 22:5n-6 is incomplete in the cerebral cortex of developing rats (10), supplementing the deficient diets with preformed 22:5n-6 was necessary to attribute deficiencies in spatial task performances to low levels of 22:6n-3 rather than low levels of 22:6n-3 plus 22:5n-6 (13). Reports of the effect of feeding 22:5n-6 on the fatty acid composition of tissues are limited (13), with no previous studies comparing diets supplemented with 22:5n-6 (free of 22:6n-3), 22:6n-3 (free of 22:5n-6), or a combination of 22:6n-3 plus 22:5n-6.…”

1. The anticonvulsant effects of docosahexaenoic acid in rodents

“…n-6 DPA supplementation did not improve performance but resulted in the same working memory deficiency seen in DHA deficient animals (Lim et al, 2005).…”