Molecular-anatomical basis for glial biosynthesis and supply of L-serine and its possibility as a tool for neuronal regeneration

L-丝氨酸是一种非必需氨基酸，可以在我们体内合成。由糖酵解途径的中间体3-磷酸甘油酸合成，并用于合成蛋白质、其他氨基酸、膜脂质、血红素和核苷酸。越来越多的证据表明，L-丝氨酸作为胶质源性营养因子，强烈促进培养神经元的存活和分化。L-丝氨酸生物合成酶3-磷酸甘油酸脱氢酶（3 PGDH）和小的中性氨基酸转运蛋白ASCT 1已被发现在成年和发育中的啮齿动物的大脑中表达的放射状胶质细胞-星形胶质细胞谱系和嗅鞘神经胶质细胞优先。相反，这些L-丝氨酸的生物合成和转运分子在神经元和吞噬细胞中很低或检测不到。基于这些发现，我们提出，L-丝氨酸合成在这些胶质细胞和其供应附近的神经元和其他胶质细胞构成了新的代谢单位在大脑中。通过神经胶质细胞和胶质细胞的关系，神经元和吞噬细胞中的葡萄糖可以战略性地用于能量产生，而其增殖、存活、分化和功能所需的各种L-丝氨酸衍生的生物分子在放射状胶质细胞-星形胶质细胞谱系和嗅鞘胶质细胞中合成并由其提供。ASCT 1在胎儿和新生儿脑中的瞬时毛细血管表达进一步表明，除了胶质细胞的L-丝氨酸，血液传播的L-丝氨酸的主动运输将在神经发育中发挥重要作用。

L-Serine is a non-essential amino acid that can be synthesized in our body. It is synthesized from an intermediate of the glycolytic pathway, 3-phosphoglycerate, and utilized for syntheses of proteins, other amino acids, membrane lipids, heme, and nucleotides. Emerging evidence indicate that L-serine plays as a glia-derived trophic factor, which strongly promotes the survival and differentiation of cultured neurons. L-serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase (3PGDH) and small neutral amino acid transporter ASCT1 have been revealed in the adult and developing brains of rodents to be expressed preferentially in the radial glia-astrocyte lineage and olfactory ensheathing glia. In contrast, these biosynthetic and transporter molecules for L-serine are low or undetectable in neurons and phagocytic cells. Based on these findings, we propose that L-serine synthesis in these glial cells and its supply to nearby neurons and other glia constitute the novel metabolic unit in the brain. Through the neuroglial and glioglial relationships, glucose in neurons and phagocytes can be strategically used for energy production, while a variety of L-Serine-derived biomolecules required for their proliferation, survival, differentiation, and function are synthesized in and supplied from the radial glia-astrocyte lineage and olfactory ensheathing glia. A transient capillary expression of ASCT1 in fetal and neonatal brains further suggests that, in addition to the glia-home L-serine, active transport of blood-borne L-serine would play an essential role in neural development.