Background – Breast-feeding is associated with higher intelligence in later life, but the mechanisms remain unknown. The subject is controversial because it is difficult to disentangle genetic, environmental and nutritional factors. Understanding the molecular basis of learning, memory and cognitive development is one of science’s most difficult frontiers, yet of increasing clinical and public health importance. Sialic acid (Sia), a 9-carbon sugar, is a vital component of brain gangliosides and the building block of polysialic acid (PSA) on neural cell adhesion molecule (NCAM). Human milk is one of nature’s richest sources of Sia (~1 g/L), but infant formulas contain little (0~0.25g/L). Gangliosides and polysialated NCAM in the brain have an important role in cell-to-cell interactions, neuronal outgrowth, modifying synaptic connectivity, and memory formation. The alpha 2,8 sialyltransferase IV (ST8SiaIV) is one of two key enzymes for synthesizing PSA on NCAM. In rodents, the level of NCAM polysialylation increase with learning behavior. The liver can synthesise Sia from glucose, but the activity of the limiting enzyme, UDP-N-acetylglucosamine-2-epimerase (GNE) is low during the neonatal period. In rat pups, supplementation Sia has been shown to enhance learning concomitantly with increased brain ganglioside-bound and protein-bound Sia content. An exogenous source of Sia may be critical under conditions of extremely rapid brain growth, particularly during the first months after birth.
Objective – We examined the dietary may be a conditionally essential nutrient for early brain development and cognition in piglets, an animal model of human infants.
Design – Piglets (n = 54) were allocated to 1 of 4 groups fed sow’s milk replacer supplemented with increasing amounts of Sia as casein glycomacropeptide for 35 days. Learning speed and memory were assessed using an easy and difficult visual cue in an 8-arm radial maze. Brain ganglioside and sialoprotein concentrations and mRNA expression of two learning-associated genes (ST8SiaIV and GNE) were determined.
Results – In both tests, the supplemented groups learned significantly faster than the control group, with a dose- response relationship in the difficult task (P = 0.018), but not in the easy task. In the hippocampus, there were significant dose-response relationships between level of Sia supplementation and mRNA levels of ST8SiaIV (P = 0.002) and GNE (P = 0.004), corresponding to proportionate increases in protein-bound Sia concentration in the frontal cortex.
Conclusion – Sia may be a limiting nutrient in the neonatal period, facilitating optimal cognitive development in young animals. An exogenous source of Sia enhances brain development, providing a mechanism to explain the link between breast-feeding and higher intelligence.
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