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

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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.