The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system

Abstract

Background: Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are major components of the cerebral cortex and visual system, where they play a critical role in neural development. We quantitatively mapped fatty acids in 26 regions of the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA and ARA supplementation and prematurity on CNS DHA and ARA concentrations.

Methods: Baboons were randomized into a breastfed (B) and four formula-fed groups: term, no DHA/ARA (T-); term, DHA/ARA supplemented (T+); preterm, no DHA/ARA (P-); preterm and DHA/ARA supplemented (P+). At four weeks adjusted age, brains were dissected and total fatty acids analyzed by gas chromatography and mass spectrometry.

Results: DHA and ARA are rich in many more structures than previously reported. They are most concentrated in structures local to the brain stem and diencephalon, particularly the basal ganglia, limbic regions, thalamus and midbrain, and comparatively lower in white matter. Dietary supplementation increased DHA in all structures but had little influence on ARA concentrations. Supplementation restored DHA concentrations to levels of breastfed neonates in all regions except the cerebral cortex and cerebellum. Prematurity per se did not exert a strong influence on DHA or ARA concentrations.

Conclusion: 1) DHA and ARA are found in high concentration throughout the primate CNS, particularly in gray matter such as basal ganglia; 2) DHA concentrations drop across most CNS structures in neonates consuming formulas with no DHA, but ARA levels are relatively immune to ARA in the diet; 3) supplementation of infant formula is effective at restoring DHA concentration in structures other than the cerebral cortex. These results will be useful as a guide to future investigations of CNS function in the absence of dietary DHA and ARA.

Figure 1

Study timeline for the formula groups. Time is represented as days from conception (conceptual age) or adjusted to time of normal term birth. The preterm (P) groups were taken at -24 days of gestational age by Cesarean section, while the term (T) groups were born spontaneously. All groups were euthanized at 28 days adjusted age, including the breastfed group (B).

Figure 2

Baboon Neonate CNS DHA Map. Schematic diagram of four-week old baboon central nervous system with DHA concentrations color coded and ranked highest (white) to lowest (dark blue). Numbered lines in the parasagittal section refer to coronal sections; in this view, right side is shown with most of the right hemisphere removed for clarity. "Duncan" refers to Duncan's multiple range test; means sharing a line are not statistically different (p < 0.05). The colors each span 10% of the DHA concentration range.

Figure 3

Baboon Neonate CNS ARA Map. Schematic diagram of four-week old baboon central nervous system with ARA concentrations color coded and ranked highest (white) to lowest (dark blue). See Figure 2 for key.