Origin and regulation of endogenous D-serine in mammalian brain tissues

点击翻译按钮获取中文摘要

Using an in vivo dialysis technique, we have studied the extracellular contents of endogenous free D-serine in comparison with that of L-serine, glycine and L-glutamate in the brain of the freely moving rat. A high amount of D-serine was detected in the dialysate obtained from the medial prefrontal cortex and striatum, whereas the cerebellar dialysate contained only a trace concentration of the D-amino acid. Intra-medial prefrontal cortex perfusion of a sodium channel activator, veratrine, augmented the extracellular release of glycine and L-glutamate but a slight decrease in that of D-serine in a tetrodotoxin-sensitive manner in the prefrontal area. Moreover, selective destruction of neuronal cell bodies in the medial frontal region by means of local infusion of an excitotoxin quinolinate resulted in a marked reduction of extracellular and tissue levels of D-serine in the infused prefrontal region. These findings suggest that endogenous Dserine might be liberated into the extracellular space from non-neuronal cells or certain exceptional neuronal cells probably by a carrier-mediated process in the mammalian prefrontal cortex . Also, the endogenous D-amino acid has been indicated to be accumulated or synthesized, at least in part, in the neuronal cells.