Oral administration of L-serine increases L- and D-serine levels in the plasma and brain of fasted rats

Ingested L-serine reduces the locomotor activity of socially isolated rats, but its effects on brain function and its underlying mechanisms of action have not yet been fully clarified. D-Serine is synthesized from L-serine by serine racemase and intraperitoneal injection of this D-amino acid attenuates depressive-like behavior in rats. We therefore hypothesized that oral intake of L-serine would stimulate the metabolism of L-serine to D-serine, and subsequently not only L-serine but also the newly formed D-serine would simultaneously affect brain functions and/or behaviors. In the present study, as the first step to test this hypothesis, L- and D-serine levels of the plasma and brain (cerebral cortex and hippocampus) were investigated at 0.5, 2, 6 and 10 h after oral administration of L-serine (6 mmol/kg) to fasted rats. In the plasma, the levels of both L-serine and D-serine were significantly increased at 0.5 h compared to control rats and thereafter their levels gradually decreased over time and had returned to the control values by 10 h. In both the cerebral cortex and the hippocampus, the increase in the level of L-serine paralleled the increase in the plasma L-serine level, whereas the levels of D-serine increased slowly for over 10 h, resulting in a small increase in D-serine. The combined data indicate that oral intake of L-serine might influence brain functions and/or behaviors not only through activity of L-serine itself but also due to activity of its metabolite D-serine.