1997 Fiscal Year Final Research Report Summary
Evaluation of the mechanism of membrane transport of metal ions in the central nervous system
| Project/Area Number |
08457111
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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 |
Hygiene
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| Research Institution | Hokkaido University |
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Principal Investigator |
SAITO Takeshi Hokkaido University School of Medicine, Associate Professor, 医学部, 助教授 (40153811)
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| Co-Investigator(Kenkyū-buntansha) |
HOSOKAWA Toshiyuki Center for Reseach and Development in Higher Education, Hokkaido University, Ass, 助教授 (00157025)
SAITO Kazuo Hokkaido University School of Medicine, Professor, 医学部, 教授 (80000917)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Trace elements / Mechanism of transport / Brain / Aging, / Neurological dysfunction |
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| Research Abstract |
In the present study, we intended to evaluate the mechanism of membrane transport of metal ions in the central nervous system and its relation to the neurotransmission. Results obtained in the present investigations are as follows ;
1.We determined concentrations of trace elements and neurotransmitters (norepinephrine (NE) , dopamine (DA) ) and its metabolites in the brain of LEC rat ; an animal model of Wilson disease. NE depression as well as accumulation of DA in the cerebral cotex of the LEC rat occurred at a young age. These alterrations of the catecholamine metabolism at a young age may be due to the depression of DBH activity induced by Cu deficiency in this region. Our results suggest the hypothesis that neurochemical changes induced by brain Cu deficiency in the early stage of Wilson disease may be involved in the neurological disturbances in patients with this disease before excessive Cu accumulation in the brain.
2.Distribution of ATP7B,the copper-transporting protein responsible for Wilson disease, was determined in various organs of the LEA rat. ATP7B was detected in several neuronal cell groups such as pyramidal cells of CA1 to CA4 and granular cells of the dentate gyrus in the brain and the renal cortex of the kidney. These results suggest that ATP7B plays an important role in the regulation of Cu homeostasis and biosynthesis of holo-Cu-binding proteins in tissues.
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