Abstract
Polyunsaturated fatty acids serve multiple functions in neurodevelopment and neurocognitive function. Intravenous lipid emulsions are administered to children that are dependent on parenteral nutrition to provide the essential fatty acids needed to sustain growth and development. One of these emulsions, derived from fish-oil, is particularly poor in the traditional essential fatty acids, linoleic and alpha-linolenic acids. However, it does contain adequate amounts of its main derivatives, arachidonic acid (ARA) and docosahexaenoic acid (DHA), respectively. This skewed composition has raised concern about the sole use of fish-oil based lipid emulsions in children and how its administration can be detrimental to their neurodevelopment. Using a custom-made diet that contains ARA and DHA as a sole source of polyunsaturated fatty acids, we bred and fed mice for multiple generations. Compared to adult, chow-fed mice, animals maintained on this special diet showed similar outcomes in a battery of neurocognitive tests performed under controlled conditions. Chow-fed mice did perform better in the rotarod test for ataxia and balance, although both experimental groups showed a conserved motor learning capacity. Conversely, mice fed the custom diet rich in DHA and ARA showed less neophobia than the chow-fed animals. Results from these experiments suggest that providing a diet where ARA and DHA are the sole source of polyunsaturated fatty acids is sufficient to support gross visual, cognitive, motor, and social development in mice.
Highlights
Essential fatty acids (EFA) are structural components of cell membranes and play key roles in cell signaling, immune function, and brain development during gestation and early postnatal life (Innis, 2007)
Overall observational scores ranged from 9 to 12 for all animals in both groups, and mean scores were similar between CHOW and docosahexaenoic acid (DHA)/arachidonic acid (ARA)
Visual acuity was similar between groups, with CHOW and DHA/ARA demonstrating similar mean acuity scores (0.395 ± 0.001 c/d vs. 0.393 ± 0.002 c/d, respectively, P = 0.40) (Figure 2)
Summary
Essential fatty acids (EFA) are structural components of cell membranes and play key roles in cell signaling, immune function, and brain development during gestation and early postnatal life (Innis, 2007). EFA cannot be synthesized in the body from simple carbon precursors and must be consumed in the diet to sustain cell growth and reproduction (Holman, 1958). Recent studies have shown that their respective downstream metabolites, the long-chain polyunsaturated fatty acids (LC-PUFA) docosahexaenoic acid (DHA) and arachidonic acid (ARA), are sufficient to sustain growth and reproduction in mammals without the development of essential fatty acid deficiency (EFAD) (Gura et al, 2005; Strijbosch et al, 2008; Le et al, 2009; de Meijer et al, 2010; Anez-Bustillos et al, 2017; Harauma et al, 2017). Since lipid emulsions have been linked to the development of this condition, a parenteral fish oil-based lipid emulsion (FOLE) has emerged as a safe and efficacious alternative for its treatment (Gura et al, 2008; Puder et al, 2009; Lam et al, 2014; Premkumar et al, 2014)
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