| Project/Area Number |
01570517
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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 University of Tokyo |
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Principal Investigator |
SAKAKIHARA Yoichi University of Tokyo, Faculty of Medicine, Department of Pediatrics, Lecturer, 医学部(病), 講師 (10143463)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Makiko University of Tokyo, Faculty of Medicine, Department of Pediatrics, Clinical ass, 医学部(病), 助手 (20225733)
KOBAYASHI Miyuki University of Tokyo, Faculty of Medicine, Department of Pediatrics, Clinical ass, 医学部(病), 助手 (60205391)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | aging / membrane fluidity / platelets / Alzheimer disease / Rett syndrome / 脳変性疾患 / 蛍光異方性 / アルツハイマ-病 / トリグリセリド / 動脈硬化 / 螢光異方性 / Cー6グリア / シナプトソ-ム膜 / ドリコ-ル |
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| Research Abstract |
The physiological properties of cellular membrane have determined many important cellular function by regulating cell motility, adhesion to the substrate, and the affinity of receptor to the ligands. The membrane fluidity is one of such physiological properties of cellular membrane, and has been studied extensively. We have measured the membrane fluidity of platelet in patients with neurodegenerative disorders, since platelet membrane shares many receptors with neurons and could be a good model to probe the changes in neuronal function.
We used steady state anisotropy of a lipophilic membrane probe, diphenylhexatrien, to monitor the changes in membrane fluidity. Using this probe, we measured the membrane fluidity of the platelet derived from patients with Alzheimer disease and Rett syndrome. It was found that the membrane fluidity in the platelet derived from the patients with Alzheimer disease was higher (more fluid) than those from age matched control. Recently, it was found that apop
… More
rotein E in patients with Alzheimer disease is abnormal. The abnormal increase in platelet membrane fluidity might be relevant to apoprotein abnormality. The membrane fluidity of platelet from Rett syndrome was not different from the control.
Since the lipid environment of platelet might alter their membrane fluidity, we next investigated the effect of plasma triglyceride on platelet membrane fluidity. We incubated human platelet with high concentration of triglyceride emulsion. It was clearly shown that the presence of triglyceride in the incubation medium has increased platelet membrane fluidity. In order to further delineate the mechanism of triglyceride action on platelet membrane, we measured the content of cholesterol in the platelet membrane. Cholesterol is one of the major determinant of cellular membrane fluidity along with fatty acid carbon chain length. It was shown that platelet membrane cholesterol decreased when the platelet were incubated with high concentration of triglyceride.
As mentioned earlier, platelet membrane shares many receptors with neuronal plasma membrane. The altered lipid environments as happened in some inborn errors of lipid metabolism, might alter membrane properties of neuron, and thus changes neuronal function.
It is implicated that measuring platelet membrane fluidity could give us important information on the function of neuronal membrane as well. Less
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