The importance of nucleoside metabolism in brain followed the recognition that i) adult
nervous system maintains its nucleotide pools in the proper qualitative and quantitative balance by salvaging
preformed purine and pyrimidine rings, rather than by synthesizing nucleosides de novo from
simple precursors, ii) adenosine, a purine nucleoside, acts as an extracellular signal, and exerts its protective
effects by interacting with plasmamembrane bound purinergic G-protein coupled P2X receptors.
More recently uridine, a pyrimidine nucleoside, has received considerable attention. Most of the
uridine content of brain is supplied by its uptake from the plasma. An increasing body of evidence
suggests that uridine exerts its function intracellularly in three distinct ways. It is phosphorylated to
UTP, a pyrimidine nucleotide acting as a precursors for RNA and DNA synthesis, and as an extracellular neurotrophic
signal. In combination with the -3 fatty acid decosahexaenoic acid and choline, uridine accelerates formation of synaptic
membrane, being an obligatory precursor for CDP-choline synthesis. Finally, uridine can preserve the ATP pool via the
conversion of its ribose-1-phosphate moiety into energetic intermediates of glycolysis. This article summarizes our present
knowledge on uridine metabolism in the brain, with special emphasis on the mechanisms maintaining its intracellular
homeostasis and on the cross talk between intracellular and extracellular uridine metabolism.