Molecular Mechanism Underlying Sialic Acid As an Essential Nutrient for Brain Development and Cognition

The early stages of neurodevelopment in infants are crucial for establishing neural structures and synaptic connections that influence brain biochemistry well into adulthood. This postnatal period of rapid neural growth is of critical importance for cell migration, neurite outgrowth, synaptic plasticity, and axon fasciculation. These processes thus place an unusually high demand on the intracellular pool of nutrients and biochemical precursors. Sialic acid (Sia), a family of 9-carbon sugar acids, occurs in large amounts in human milk oligosaccharides and is an essential component of brain gangliosides and sialylated glycoproteins, particularly as precursors for the synthesis of the polysialic acid (polySia) glycan that post-translationally modify the cell membrane-associated neural cell adhesion molecules (NCAM). Human milk is noteworthy in containing exceptionally high levels of Sia-glycoconjugates. The predominate form of Sia in human milk is N-acetylneuraminic acid (Neu5Ac). Infant formula, however, contains low levels of Sia consisting of both Neu5Ac and N-glycolyneuraminic acid (Neu5Gc). Current studies implicate Neu5Gc in several human inflammatory diseases. Polysialylated NCAM and neural gangliosides both play critical roles in mediating cell-to-cell interactions important for neuronal outgrowth, synaptic connectivity, and memory formation. A diet rich in Sia also increases the level of Sia in the brains of postnatal piglets, the expression level of 2 learning-related genes, and enhances learning and memory.