1988 Fiscal Year Final Research Report Summary
Study on aging of the nervous tissue and the endogeneous toxic substances
| Project/Area Number |
62480207
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
GOTO Ikuo Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (20038631)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Takuro Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (40158902)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Aging / toxic substance / psychosine / sphingosine / リゾスルファチド |
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| Research Abstract |
Endogeneous toxic substance may cause the aging of the nervous tissue. It is well known that lysosphingolipids, deacylated forms of sphingolipids which are abundant in the nervous tissur, are highly toxic. We have developed assay methods of lysosphingolipids, and investi- gated metabolisms and biological functions of the lipids these two years. The principle of the assay method is to couple fluorescent probe with the primary amine in lysosphingolipids and to detect fluorescent lysosphingolipids using high-performance liquid chromatography. Using this method, we demonstrated an occurrence of free sphingoid base and galactosylsphingo-sine (psychosine) in normal mouse and human tissues. Concentrations of psychosine increased with age, while those of free sphingoid bases did not change during developmental periods. Further studies on the concentration of lysosphingolipids in nervous tissues of aged human or animal subjects are currently under way.
As to the toxicity of lysosphingolipids, we found a close relationship of psychosine accumulation and the demyelination, occurring in globoid cell leukodystrouphy. In the twitcher mouse, an animal model of human globoid cell leukodystrophy, fatty acylation of myelin proteo-lipid protein was desturbed, probably because of an accumulation of spychosine in the myelin. We reported that lysosulfatide inhibited cytochrome C oxidase activity.
Further studies concerning physiological functions and metabolisms of lysosphingolipids in tissues from normal and aged subjects will be necessary.
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