| Project/Area Number |
11680777
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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 | Institute for Development Research, Aichi Human Service Center |
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Principal Investigator |
KATOH Ritsuko Institute for Development Research, Aichi Human Service Center, Department of Perinatology, Room Chief, 周生期学部, 室長 (80100163)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Brain-derived neurotrophic factor / Neurotrophin-3 / Nerve growth factor / Hippocampus / Cerebellum / Granule cells / Proliferation / Apoptosis / リルゾール / 神経前駆細胞 / けいれん誘発物質 / イオンチャネル / ラット / 細胞分裂 |
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| Research Abstract |
There are four kinds of neurotrophins in mammals and each neurotrophin is considered to play its own roles in the limited regions and at the specific developmental stages. We have established enzyme immunoassay systems for such neurotorphins and have examined their distribution in rats. Here, we searched for compounds that stimulate brain-derived neurotorphic factor (BDNF) synthesis in the rat hippocampus because its level markedly decreases in Alzheimer's disease. Some of antibodies against neurotrophins prepared blocked the biological activities of respective neurotrophins. Therefore, to investigate functions of neurotrophins in the brain, we injected such antibodies into the lateral ventricle and observed subsequent morphological changes in the brain.
(1) An intraventricular injection of anti-neurotrophin-3 antibodies inhibited proliferation of cerebellar granule precursors and caused cell death of mature granule neurons and Bergmann glial cells. Effects on granule neurons were observed at specific lobules and those on glial cells were observed in all lobules.
(2) The majority of the compounds tested stimulating BDNF synthesis in the rat hippocampus caused cell death, while riluzole enhanced BDNF production in this region without inducing cell death.
(3) Repeated injections of riluzole cause a persistent increase in BDNF levels and promoted proliferation of newly generating cells in the adult rat hippocampus. It was also demonstrated that BDNF is necessary for the promotion.
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