| Project/Area Number |
07680897
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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 |
神経・脳内生理学
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| Research Institution | Nagoya City University |
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Principal Investigator |
FUKUDA Atsuo Nagoya City Univ., Medical School, Assoc. Prof., 医学部, 助教授 (50254272)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Ichiro Nat'l. Inst. Physiol. Sci., Neuroinfo., Instructor, 神経情報, 助手 (70264710)
NISHINO Hitoo Nagoya City Univ., Medical School, Professor, 医学部, 教授 (60073730)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Parkinson disease / Cerebral ischemia / 3-Nitropropionic acid / Intracellular Ca / Cerebral Cortex / Striatum / Neural transplantation / Cell death / 脳移植 / シナプス / 黒質 / パッチクランプ |
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| Research Abstract |
(1) Preparing Model Rats of Diseases of the Central Nervous System : Hemiparkinsonian disease model rats were made with unilateral injection of 6-OHDA to substantia nigra. Cerebral ischemia was performed by unilateral mid cerebral artery occlusion in adult rats and by unilateral common carotid artery ligation with hypoxia (8% oxygen) in immature rats. 3-Nitropropionic acid was administered intraperitoneously to induce Huntington diesease-like symptoms and striatal lesions in rats.
(2) In Vitro Model of the Diseases Described Above : Cerebralischemia was simulated by oxygen-glucose deprivation of neocortical slices. LayrII/III pyramidal cells were more vulnerable to Ca^<2+>-overload than those in the other layrs due to NMDA receptor susceptibility. We also found that GABA may aggravate ischemic damage directly and/or via mediation of glutamate-NMDA excitotoxicity as a result of E_<el> shift during ischemia. Perfusion of cultured striatal and cortical glial cells with 3-nitropropionic aci
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d caused cellular Ca^<2+>-overload leading to necrotic deathby reverse operation of Na^+-Ca^<2+> exchanger.
Physiological Experiments on Transplanted Neurons in Brain Slices from the Model Rats : We established methods for labeling and identification of living donor cells in brains slices of recipient himiparkinsonian and cerebral ischemia model rats. Voltage dependent Na^+ and K^+ currents as well as glutamate-induced intracellular Ca^<2+> increase were successfully recorded from the grafted cells identified by the labeling. Interconnection between the host and grafted cells was functionally proved in brain slices as intracellular Ca^<2+> transients in response to the electrical stimulation of neighboring host tissue.
Detection of Gene Expression Induced in the Model Rats : In the 3-nitropropionic acid-induced Huntington disease-like striatal lesion, expression of iNOS mRNA increased as revealed by RT-PCR method Immunohistochemical staining also showed an increased level of iNOS in parallel with mRNA. Less
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