| Project/Area Number |
10214201
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (B)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Hokkaido University |
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Principal Investigator |
WATANABE Masahiko Hokkaido Univ., School of Medicine, Professor, 大学院・医学研究科, 教授 (70210945)
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| Co-Investigator(Kenkyū-buntansha) |
高山 千利 北海道大学, 医学部, 講師 (60197217)
永島 雅文 北海道大学, 医学部, 助教授 (40241319)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥28,700,000 (Direct Cost: ¥28,700,000)
Fiscal Year 2001: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1998: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | Bergmann glia / Purkinje cell / Cerebellum / Development / Dendrite / Serine / Mouse / 3PGDH / セリン合成 / 星状膠細胞 / 嗅神経被覆グリア / グルタミン酸トランスボーター / GLAST / シナプス形成 / グルタミン酸トランスポーター |
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| Research Abstract |
The Bergmann glia (BG) is unipolar cerebellar astrocytes associating with migrating granule cells (GCs) and mature Purkinje cells (PCs). By taking cytochemical advantage of glutamate transporter GLAST localized on the plasmalemma of raidal glia/astrocyte lineage, we analyzed the morphodifferentiation of BG. Cells expressing GLAST mRNA were present only in the ventricular zone at embryonic day 13 (El3). At E14, they first appeared in the mantle zone, where they had oval to elongated cell bodies and radial fibers reaching the pial surface, suggesting the migration of cerebellar radial glia. From E18 to P7, GLAST-expressing cells in the cortex established characteristics of BG (i.e., monolayer alignment around PC bodies and expression of glial fibrillary acidic protein in Bergmann fibers) and further up-regulated GLAST expression, whereas those in other cerebellar regions were changed into multipolar astrocytes and down-regulated the expression. From P7 to P21, Bergmann fibers were change
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d from linear to reticular form in a deep-to-superficial gradient; the superficial linear portion was intimately contacted with the growing tips of PC dendrites, while the deeper reticular portion reflected active formation of membranous protrusions invading the neuropil elaborately to surround PC synapses. Following the accomplishment as unipolar cortical astrocytes, therefore, Bergmann fibers of BG undergo dynamic transformation in the active synaptogenic phase, leading to structural maturation of PC synapses. Intimate contacts with dendritic tips further suggest that Bergmann fibers could be a structural substrate for arborizing PC dendrites as well as for migrating GCs.
To further pursue the molecular basis, neuron-glial relationship on serine metabolism was examined by producing antibody to serine synthetic enzyme 3-phosphoglycerate dehydrogenase (3PGDH). 3PGDH was highly and selectively expressed throughout development in astrocytes and olfactory ensheathing glia. In the cerebellum, the growing tips of 3PGDH-negative PC dendrites were contacted to 3PGDH-positive Bergmann fibers in developing cerebellum. These results suggest that serine biosynthesis by BG and its supply to PCs are one of the plausible reason for the intimate structural relationships between dendrites and glial fibers during development. Less
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