| Project/Area Number |
05044193
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | The Institute of Chemical and Physical Research |
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Principal Investigator |
HIRABAYASHI Yoshio The Institute of Chemical and Physical Research, 国際フロンティア, 研究員 (90106435)
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| Co-Investigator(Kenkyū-buntansha) |
LI Yu-teh Tulane University School of Medicine, 医学部, 教授
MIZOGUCHI Tsugio Tokai University, 工学部, 教授 (90133149)
FURUYA Shigeki The Institute of Chemical and Physical Research, 国際フロンティア, 研究員 (00222274)
YUーTEH Li チューレン大学, 医学部, 教授
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Ganglioside / Cholinergic Neuron / Sialic Acid / Sialyltransferase / ニューロン / ポリシアル酸 / 単クローン抗体 |
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| Research Abstract |
Ganglioside are sialic acid containing glycosphingolipids found in highest concentration in the central nervous system (CNS) tissues. We found that more than 100 species including extremely minor species exist in CNS.Among gangliosides isolated by using a new column chromatographic method, a unique and new series of gangliosides was shown to exist in polysialoganglioside fraction. They possessed N-acetylneuraminic acid attached to N-acetylgalactosamine in alpha2-6 linkage.
The immunohistochemical staining of human and rat brains with specific monoclonal antibodies to the gangliosides showed that they are expressed in region-or neuronal cell type-specific manner. For example, GD1alpha was highly enriched in cerebellar Purkinje cells. GQ1balpha was expressed in the cholinergic nerve terminals.
We have demonstrated that GT1aalpha and GQ1balpha was synthesized from GD1a and GT1b, respectively, by the action of a GalNAc alpha2-6sialyltransferase. Once gangliosides were sialylated by the enzyme, further sialylation of the gangliosides could not proceed.
To understand a physiological function of sphingolipids, we have developed a dissociated cell culture system of rat cerebellum. In our culture system, Purkinje cells developed well-differentiated dendrites and axons. Addition of a inhibitor of ceramide synthase (fumonisin B1) resulted in impairment of dendrite formation. In contrast, granule cells appeared to be almost normal following treatment with the inhibitor. These results show that sphingolipids serve as an essential component for the differentiation and maintenance of the dendritic arborizations of cerebellar Purkinje cells. Further studies of the molecular mechanism by which sphingolipids contribute to the dendrite growth and survival of neurons will be needed.
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