Free d-aspartate is abundant in the mammalian embryonic brain. However, following the postnatal onset of the catabolic d-aspartate oxidase (DDO) activity, cerebral d-aspartate levels drastically decrease, remaining constantly low throughout life. d-Aspartate stimulates both glutamatergic NMDA receptors (NMDARs) and metabotropic Glu5 receptors. In rodents, short-term d-aspartate exposure increases spine density and synaptic plasticity, and improves cognition. Conversely, persistently high d-Asp levels produce NMDAR-dependent neurotoxic effects, leading to precocious neuroinflammation and cell death. These pieces of evidence highlight the dichotomous impact of d-aspartate signaling on NMDAR-dependent processes and, in turn, unveil a neuroprotective role for DDO in preventing the detrimental effects of excessive d-aspartate stimulation during aging. Here, we will focus on the in vivo influence of altered d-aspartate metabolism on the modulation of glutamatergic functions and its involvement in translational studies. Finally, preliminary data on the role of embryonic d-aspartate in the mouse brain will also be reviewed.

游离d-天冬氨酸在哺乳动物胚胎脑中丰富。然而，在产后分解代谢的d-天冬氨酸氧化酶（DDO）活性发作后，脑d-天冬氨酸水平急剧下降，终生始终保持较低水平。d-天冬氨酸刺激谷氨酸能的NMDA受体（NMDARs）和代谢型的Glu5受体。在啮齿动物中，短期d-天冬氨酸暴露会增加脊柱密度和突触可塑性，并改善认知能力。相反，持续高的d -Asp水平会产生NMDAR依赖性神经毒性作用，导致性早熟神经炎症和细胞死亡。这些证据突出了d的二分影响-天冬氨酸信号转导依赖于NMDAR的过程，进而揭示了DDO在防止衰老过程中过量的d-天冬氨酸刺激的有害作用方面的神经保护作用。在这里，我们将集中研究改变的d-天冬氨酸代谢对谷氨酸能功能的调节及其参与翻译研究的体内影响。最后，还将回顾有关胚胎d-天冬氨酸在小鼠脑中的作用的初步数据。