1989 Fiscal Year Final Research Report Summary
The Pathogenesis of Demyelination in Krabbe's disease and it's therapy
| Project/Area Number |
63570456
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | The Jikei University School of Medicine, Department of Pediatrics |
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Principal Investigator |
TOKORO Toshiharu The Jikei Univ. Sch. of Med., Clinical fellow, 小児科, 助手 (40112841)
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| Co-Investigator(Kenkyū-buntansha) |
UMEZAWA Fusayo 東京慈恵会医科大学, 小児科, 助手 (50185063)
SEKIGUCHI Shigeru 東京慈恵会医科大学, 小児科, 助手 (90119818)
IDA Hiroyuki 東京慈恵会医科大学, 小児科, 助手 (90167255)
ITO Fumiyuki 東京慈恵会医科大学, 小児科, 助教授 (10057010)
ETO Yoshikatsu The Jikei Univ. Sch. of Med. Department of Pediatrics, 小児科, 助教授 (50056909)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Krabbe's disease / Psychosine / Twitcher mouse / Niemann-Pick mouse / Lysosomal disorder |
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| Research Abstract |
We investigated the pathogenesis of demyelination in Krabbe's disease using Twitcher mouse and the cholesterol metabolism in Niemann-Pick mouse model.
1. Marked accumulation of psychosine was found in the Twitcher mouse Dorsal Root Ganglion. And psychosine played an important role for the demyelination in Floboid Cell Leukodystrophy.
2. Psychosine inhibited the incorporation of H-galactose into cerebroside and sulfatide in cultured colgodendroglia. This results suggested that psycgosine participate in the demyelination in vitro.
3. Psychosine treated cells showed destruction of cytoskeleton and suggested that psychosine influences mitochondrial function, possibly through the inhibition of oxidative phosphorylation.
4. Liposomes prepared from p-aminophenyl-alpha-mannoside were sufficiently incorporated into the mouse brain across the blood brain barrier. It was suggested that glial cell recognize mannose molecude on the surface of the membrane.
5. It was found that the exogenous cholesterol esterification was found in Niemann-Pick mouse fibroblasts. The impaired cholesterol esterification might be an important role for the pathogenesis of Niemann-Pick mouse model.
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