| Project/Area Number |
10557061
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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 | 展開研究 |
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| Research Field |
Neurology
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| Research Institution | Hiroshima University |
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Principal Investigator |
NAKAMURA Shigenobu Hiroshima University, Professor, 医学部, 教授 (30026843)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Hideshi Hiroshima University, Assistant, 医学部, 助手 (70253060)
MIYAMOTO Masaomi Takeda Farmaceutical Industry, Chief Researcher, 創薬研究本部, 主席研究員
SASA Masashi Hiroshima University, Professor, 医学部, 教授 (20025654)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | Alzheimer's disease / Parkinson's disease / glutamic acid / neuronal death / glutamate transporter / L-2-(carboxycyclopropyl)-glycine / reverse transpot / sodium ion / 海馬CA1領域 / GLT1 / GluT1 / bromocriptine / ergotamine / エルゴット・アルカロイド / 海馬 / 前頭葉 / 小脳 |
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| Research Abstract |
Neurodegenerative diseases such as Alzheimer's disease or Parkinson' s disease are caused by loss of neuronal cells. The influx of calcium ion produced by an excessive stimulation of glutamic acid is postulated as a major factor related with neuronal death. The release of glutamic acid has been a candidate for the origin of synaptic glutamic acid. Our previous studies have revealed that the alteration of extracellular ion concentrations results in the release of intracellular glutamate into the synaptic space. In acute phase of cerebral ischemia or head trauma, neural cells are damaged and produce an abnormal ion concentrations in and outside of the cell. Extracellular concentrations of sodium decreases and those of potassium increases. These ionic changes lead a reverse transport of glutamate. Glutamate transporter incorporated glutamate into the cell from the medium in normal conditions, while glutamate transporter released glutamate from the cell under the low concentration of extracellular sodium ion, introducing neuronal death. Therefore, we investigated drugs which inhibit the glutamate release through a reverse glutamate transport by glutamate transporter. WC found that an analogue of glutamic acid, L-2-(carboxycyclopropyl)-glycine (L-CCG) has four isomers, I-IV.Among 4 isomers, L-CCG III and IV inhibited the release of glutamate. These substances might serve as a possible drug to prevent neuronal death after the head trauma or ischemia. We further continue to find out a better analogue which inhibit a reverse transport of glutamic acid in the pathological conditions.
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