In vivo evidence for the link between L- and D-serine metabolism in rat cerebral cortex

To obtain an insight into the metabolic pathways of endogenous D-serine in mammalian brains, we have investigated in the infant rat the effects of systemic administration of L-serine, D-serine, and related amino acids, including glycine and threonine, on the amino acid contents in the cerebral cortex. Intraperitoneal injection of L-serine induced a rapid and transient elevation of the levels of L-serine itself in the neocortex, with its peak at 3 h post injection, and a delayed and prolonged increase in D-serine contents from 1.5 h to at least 24 h thereafter. Similarly, a significant augmentation in cerebral D-serine contents was observed 6 h after intraperitoneal administration of glycine, which also elevated the cortical L-serine levels. In contrast, L-threonine injection affected the concentrations of neither D- nor L-serine in the cortex of the pups. D-Serine given systemically, in turn, increased the neocortical contents of L-serine as well as D-serine itself, but failed to alter those of glycine and L-threonine. These in vivo data suggest the possible link between metabolic pathways of D- and L-serine in the cerebral cortex of the rat.