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L-Ser
is a Key Mediator of the Astroglial Trophic Action on Cerebellar Purkinje Cells
Neuronal Circuit Mechanism
Research Group |
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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. |
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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
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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)
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