Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents

Abstract

The brain is unusual among organs in that the rates of many of its characteristic enzymatic reactions are controlled by the local concentrations of their substrates, which also happen to be nutrients that cross the blood-brain barrier. Thus, for example, brain levels of tryptophan, tyrosine, or choline can control the rates at which neurons synthesize serotonin, dopamine, or acetylcholine, respectively. The rates at which brain cells produce membrane phospholipids such as phosphatidylcholine (PC) are also under such control, both in adult animals and, especially, during early development. If pregnant rats are fed the 3 dietary constituents needed for PC synthesis- docosahexaenoic acid, uridine, and choline-starting 10 days before parturition and continuing for 20 days during nursing, brain levels of PC, and of the other membrane phosphatides (per cell or per mg protein), are increased by 50% or more. In adult animals, this treatment is also known to increase synaptic proteins (eg, synapsin-l, syntaxin-3, GluR-l, PSD-95) but not ubiquitous proteins like beta-tubulin and to increase (by 30% or more) the number of dendritic spines on hippocampal neurons. Docosahexaenoic acid currently is widely used, in human infants, to diminish the negative effects of prematurity on cognitive development. Moreover, docosahexaenoic acid, uridine (as uridine monophosphate), and choline are all found in mother's milk, and included in most infant formulas. It is proposed that these substances are part of a regulatory mechanism through which plasma composition influences brain development.