| Project/Area Number |
11680771
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY |
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Principal Investigator |
UCHIDA Yoko TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, DEPARTMENT OF NEUROPATHOLOGY, RESEARCH SCIENTIST, 神経病理部門, 研究員 (60133633)
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| Co-Investigator(Kenkyū-buntansha) |
GOMI Fujiya TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, DEPARTMENT OF ULTRASTRUCTURE RESEARCH ASSOCIATE, 神経病理部門, 研究員 (40205620)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | β-amyloid / neurotoxicity / MAP1B / fetal antigens / 神経細胞死 / 胎児性抗原 |
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| Research Abstract |
To define fetal genes associated with neuronal death by amyloid β protein (Aβ), we analyzed gene expression in rat cerebral cortical neurons treated with A β 1-42 peptide using macro array on which 1176 cDNAs were spotted. Seventy eight mRNAs were induced in cortical neurons treated with Aβ. Out of 78 mRNAs induced by A β treatment, 10 mRNAs were upregulated in fetal (E20 days) cerebral cortex. These genes include molecules implicated in neurite outgrowth during development or responsible for regulating neurotransmitter release. MAP1B, identified as the gene highly expressed both in fetal and in A β-treated neurons, is a component of paired helical filament in Alzheimer's brain. There are three transcripts in MAP1B.Alternative transcript started from exon 3U increased in neurons treated with A β. This transcript is translated into N-terminal Δ126 amino acid truncated MAP1B.To define the role of 2 kind of MAP1B isoforms for neurite outgrowth and neuronal death, the N-terminal truncated or full-length MAP1B were overexpressed in cortical neurons. Cortical neurons expressing the truncated form had shorten and less branched neurites than those expressing full-length form. Overexpression of truncated form did not influence the neuronal death by serum withdrawal. In contrast, overexpression of full-length form resulted in promotion of neurite outgrowth and neuronal death by serum withdrawal. These results indicated that induction of alternative transcripts of MAP1B in neurons may be a protective response in brain.
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