| Project/Area Number |
18500246
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Aoyama Gakuin University |
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Principal Investigator |
FUKUOKA Shinichi Aoyama Gakuin University, College of Science and Engineering, Professor (20183923)
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| Co-Investigator(Kenkyū-buntansha) |
ARII Yasuhiro Aoyama Gakuin University, College of Science and Engineering, Assistant Professor (60360484)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | tryptophan / quinolinate / QPRT knockout mice / neurodegeneration / QPRT / 神経細胞変性疾患 / トリプトファン代謝 |
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| Research Abstract |
Quinolinic acid (QA) is an intermediate metabolite in the tryptophan (Trp)-NAD pathway. QA is an excitatory neurotoxin acting on N-methyl-D-aspartic acid receptor (NMDAR). In general, QA is metabolized by Quinolinatephosphoribosyltransferase (QPRT) and the concentration of QA in the brain is very low. But it is increased in the neurodegenerative disease such as Huntington's disease (HD) and Alzheimer's disease. Therefore it is considered that QA is involved in the pathogenesis of neurodegenerative disease (Quinolinate hypothesis). In this study we have established a QPRT knockout mice (KO mice).
To analyze the effect of QPRT gene deletion and excessive intake of Trp, we divided 4 weeks old WT mice and KO mice into the control group and the Trp supplemented (control diet +2%Trp) group and measured food consumption and body weight for 4 weeks. we isolated mice cerebrum and analyzed gene expression levels using real-time PCR. Target genes are Indoleamine 2,3-dioxygenase (IDO) which metabol
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izes Trp、 Aminocarboxymuconatesemialdehydedecarboxylase (ACMSD) which inhibits the production of QA Nitric oxide synthase (NOS) which is activated by QA、No significant differences in food consumption and body weight were found between different genotypes and diets. Therefore this result suggests that QPRT gene deletion and excessive intake of Trp don't influence growth. No significant differences in the expression of IDO were found between different genotypes and diets, so this result suggests that Trp is normally metabolized in KO mice. No significant differences in the expression of ACMSD and NOS were found between different genotypes and diets, but both of which in the Trp supplemented group were non-significantly increased in comparison to the control group. Consequently, this result suggests that the production of QA is inhibited by ACMSD in the Trp supplemented group because the concentration of QA is increased. Because a certain type of abnormal behaviors were observed, we assume that the accumulation of QA is progressively occured in the KO mice. Less
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