L-Ser is a Key Mediator of the Astroglial Trophic Action on Cerebellar Purkinje Cells Neuronal Circuit Mechanism Research Group Astroglial cells have been considered to play an important role in the survival/development and functional expression of neurons, but little is known about molecules involved in these processes. In this study, Dr. Shigeki Furuya and Dr. Yoshio Hirabayashi in the Neuronal Circuit Mechanism Research Group, worked in collaboration with Kanazawa University, Hokkaido University and Yokohama City University, reveal that L-serine (L-Ser) is an essential astroglia-derived factor for the survival, dendritogenesis, and membrane excitability of cerebellar Purkinje cells (see Fig. A-C). The trophic activity of L-Ser is stronger than those of any other known protein neurotrophic factors. What is the mechanism underlying the L-Ser trophic action? In textbooks of biochemistry, L-Ser is generally classified as a member of nonessential amino acids. This means that all cells can synthesize L-Ser by themselves. However, they demonstrate that Purkinje cells do not express 3-phosphoglycerate dehydrogenase (3PGDH), a key enzyme for the biosynthesis of L-Ser. By contrast, the Bergmann glia, a surrounding astroglial cell, highly expresses 3PGDH mRNA and protein (Fig. D). These findings suggest that Purkinje cells depend on astroglial cells for the supply of L-Ser as an essential amino acid. These findings will bring about novel insights into trophic/molecular communication between neurons and glia in the central nervous system and the development of pharmaceutical applications and therapies. A: L-Ser dramatically improves the survival of Purkinje cells. B: L-Ser also promotes the development of dendrites. C: Differences in firing patterns in response to depolarizing current stimuli. The firing pattern remains immature in cells grown without L-Ser treatment. D: Bergmann glia-enriched expression of 3PGDH, a key enzyme for the biosynthesis of L-Ser (red: 3PGDH, green: calbindin) magnified scene by clicking image Furuya, S., Tabata, T., Mitoma, J., Yamada, K., Yamasaki, M., Makino, A., Yamamoto, T., Watanabe, M., Kano, M., Hirabayashi, Y. L-Ser and Gly serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons. Proc. Natl. Acad. Sci. USA Vol. 97, pp. 11528-11533, October (2000)