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

本文用活体透析技术研究了自由活动大鼠脑内细胞外游离D-丝氨酸与L-丝氨酸、甘氨酸、L-谷氨酸的含量。内侧前额叶皮质和纹状体的透析液中含有大量的D-丝氨酸，而小脑透析液中只含有微量的D-氨基酸。内侧前额叶皮质灌流钠通道激动剂藜芦碱，以河豚毒素敏感的方式增加细胞外甘氨酸和L-谷氨酸的释放，但轻微减少D-丝氨酸的释放。此外，通过局部注射喹啉酸类兴奋性毒素选择性破坏额叶内侧区神经元胞体，可显著降低前额叶灌注区的细胞外和组织内D-丝氨酸水平。这些发现表明，内源性Dserine可能从非神经细胞或某些特殊的神经细胞释放到细胞外空间，可能是通过载体介导的哺乳动物前额叶皮质的过程。此外，已表明内源性D-氨基酸至少部分地在神经细胞中积累或合成。

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.