Small Changes of Dietary (n-6) and (n-3)/Fatty Acid Content Ratio Alter Phosphatidylethanolamine and Phosphatidylcholine Fatty Acid Composition During Development of Neuronal and Glial Cells in Rats

Abstract

It has been suggested that the fat composition of infant formula should provide arachidonic acid [20:4(n-6)] and docosahexaenoic acid [22:6(n-3)] or increased alpha-linolenic acid [18:3(n-3)] to optimize the (n-3) and (n-6) fatty acid content of brain during infant development. This experiment examined the effects of feeding increased levels of 18:3(n-3), 20:4(n-6) and 22:6(n-3) on brain development in neonatal rats. Diets varying in (n-6) and (n-3) fatty acid content with or without 20:4(n-6) or 22:6(n-3), at levels proposed for infant formula, were fed to nursing dams from parturition and subsequently to weaned pups until 6 wk of age. Neuronal and glial cells were isolated from the frontal region, cerebellum and hippocampus of the brain. Fatty acid analyses of ethanolamine- and choline-phosphoglycerides indicated that small changes in the dietary (n-6)/(n-3) ratio significantly altered neuronal and glial membrane fatty acid composition. Brain regions and cell types varied in amount and rate of 20:4(n-6) and 22:6(n-3) accretion. Fatty acid composition of individual phosphoglycerides was distinct and exhibited changes with age. Inclusion of both 20:4(n-6) and 22:6(n-3) in the diet resulted in alteration of brain fatty acid composition reflecting the fatty acid composition of the diet. If analogous developmental changes occur in human brain, then these results imply that addition of 20:4(n-6) and 22:6(n-3) or a reduced 18:2(n-6):18:3(n-3) ratio in infant formula may result in fatty acid profiles of neuronal and glial cells in formula-fed infants similar to those observed in breast-fed infants.

Executive functions and the ω-6-to-ω-3 fatty acid ratio: a cross-sectional study

“…The children in this study who had low plasma n-3 required a lower ratio to quickly think through these most difficult problems. A high ratio with low n-3 intake represents unbalanced n-6 and n-3, which has been shown in rats and cells to result in deficiencies in cognitive performance and n-3 FAs (14,15,19,30). With the use of both dietary FAs and plasma FAs, there were opposite results with children aged 7-9 y and children aged 10-12 y.…”

“…The hippocampus accretes more n-3 than the frontal cortex (14,15); thus, hippocampal-based tasks likely will best be supported by more n-3. Less flexibility is required for the simpler problems, and the joint roles of n-6 and n-3 FAs are less obvious for these simpler tasks.…”

“…In particular, cognitive functions subserved by the hippocampus and frontal cortex, such as memory and executive functions, are sensitive to imbalances in the n-6:n-3 ratio because of the presence of high n-6 and n-3 FAs (7), as well as the role of n-6 and n-3 in neurotransmitter concentrations (8,9), receptor density and function (10,11), and neuronal growth (12,13) in those brain areas. The n-6 and n-3 FAs compete for metabolic resources; thus, an imbalance of n-6 and n-3 FAs in the diet decreases the products of one or another of the FA metabolic pathways (14)(15)(16)(17)(18). It has been found that providing a balanced n-6:n-3 ratio leads to similar concentrations of n-6 and n-3 FAs in the brain, whereas providing an imbalanced n-6:n-3 ratio produces deficiencies in n-3 FAs, regardless of the amount of specific FAs in the diet (19).…”

Essential fatty acids and the brain: possible health implications

“…Modi®cations of the brain membrane fatty acid composition have been reported with supplementation of various dietary oils [3,17,36,45,54,62,74,75,84,128,133,153,155] (Table 3). Furthermore, changes in PUFA content of microsomal and mitochondrial mem- [48], and Salem [116].…”

Docosahexaenoic acid (DHA), essentiality and requirements: why and how to provide supplementation

“…DHA is required during brain development when neuronal and glial differentiation and migration, and active myelination and synaptogenesis take place. Neuronal differentiation and migration are essentially prenatal processes (Jumpsen et al, 1997), but gliogenesis, neuronal myelination and synaptogenesis are predominantly postnatal events occurring in the first 18 months of postnatal life (Morgane et al, 1993). DHA together with AA are highly conserved LC-PUFA in the brain because less than 15% of these fatty acids is beta oxidized, in contrast to alpha linolenic acid (C18:3, omega-3, LNA) the precursor of DHA, and of linoleic acid (C18:2, omega-6, LA) the precursor of AA, which are converted in a small proportion to the respective LC-PUFA in the brain, the rest being oxidized (Leyton et al, 1987).…”