3-phosphoglycerate dehydrogenase, a key enzyme for L-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain

L-Serine is synthesized from glycolytic intermediate 3-phosphoglycerate and is an indispensable precursor for the synthesis of proteins, membrane lipi ds, nucleotides, and neuroactive amino adds D-serine and glycine. We have r ecently shown that L-serine and its interconvertible glycine act as Bergman n glia-derived trophic factors for cerebellar Purkinje cells. To investigat e whether such a metabolic neuron-glial relationship is fundamental to the developing and adult brain, we examined by in situ hybridization and immuno histochemistry the cellular expression of 3-phosphoglycerate dehydrogenase (3PGDH), the initial step enzyme for de novo L-serine biosynthesis in anima l cells. At early stages when the neural wall consists exclusively of the v entricular zone, neuroepithelial stem cells expressed 3PGDH strongly and ho mogeneously. Thereafter, 3PGDH expression was downregulated and eventually disappeared in neuronal populations, whereas its high expression was transm itted to the radial glia and later to astrocytes in the gray and white matt ers. In addition, 3PGDH was highly expressed throughout development in the olfactory ensheathing glia, a specialized supporting cell that thoroughly e nsheathes olfactory nerves. These results establish a fundamental link of t he radial glia/astrocyte lineage and olfactory ensheathing glia to L-serine biosynthesis in the brain. We discuss this finding in the context of the h ypothesis that 3PGDH expression in these glia cells contributes to energy m etabolism in differentiating and differentiated neurons and other glia cell s, which are known to be vulnerable to energy loss.