| Project/Area Number |
07458207
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Okazaki National Institutes |
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Principal Investigator |
IKENAKA Kazuhiro Okazaki National Institute for Physiological Sciences, Professor, 生理学研究所, 教授 (00144527)
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| Co-Investigator(Kenkyū-buntansha) |
KAGAWA Tetsushi Okazaki National Institute for Physiological Sciences, Research Associate, 生理学研究所, 助手 (50270484)
BABA Hiroko Okazaki National Institute for Physiological Sciences, Research Associate, 生理学研究所, 助手 (40271499)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1995: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | myelin proteolipid protein / anti-sense olilgonucleotide / phosphorothioate / gene therapy / demyelination / myelin |
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| Research Abstract |
Myelin proteolipid protein (PLP) is one of the major compornents of the myelin in the central nervous system (CNS), and the duplication of this gene cause human devastating disease, Pelizaeus-Merzbacher disease. Recently we have developed a mouse model for this disease by overexpression of PLP gene (PLP-Tg) (T.Kagawa et al.Neuron, '94). PLP-Tg shows severe dysmyelination and a short life span in the homozygote and progressive demyelination which usually starts around 6 months after birth in the heterozygote. In order to examine of the expression level of PLP gene can be altered by anti-sense oligonucleotide (AS-ODN) treatment, oligodendrocytes (OL) form E17 normal ICR mouse brain were cultured in the medium containing AS-ODN for 3 days. The treated OL showed the reduction of PLP accompanied by the apparent morphological changes with the reduction in myelin-like membranes. Thus, the expression level of PLP gene can be regualted by antisense Odn triatment. Then, the nerve conduction velosity (NCV) was measured in PLP-Tg spinal cord, and the severe conduction block was revealed in 8-months-old PLP-Tg. Since the axonal degeneration is observed only after demyelination is severely progressed, it seems to occur secondarily from this severe conduction block. Now we have plan to treat this animal with either AS-ODN to reduce the production of PLP gene, or with transplantation of OL in the CNS to protect the following axonal degeneration.
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