1998 Fiscal Year Final Research Report Summary
Study on the ischemia-induced neuronal injuries with special reference to alterations in the intracellular signaling cascades.
| Project/Area Number |
09671432
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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 |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
GOTO Satoshi Kumamoto University, University Hospital, Lecturer, 医学部・附属病院, 講師 (50240916)
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| Co-Investigator(Kenkyū-buntansha) |
NISHI Toru Kumamoto University, University Hospital, Assistant Professor, 医学部・附属病院, 助手 (00264309)
HAMADA Jun-ichiro Kumamoto University, University Hospital, Assistant Professor, 医学部・附属病院, 助手 (40253752)
USHIO Yukitaka Kumamoto University, Medical School, Professor, 医学部, 教授 (20028583)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Cerebral ischemia / N-methyl-D-aspartate / Striatum / GABA / Transplantation / Calcium signal / STEP / Tyrosine-phosphatase |
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| Research Abstract |
In a series of our experiments, we have found that N-methyl-D--aspartate (NMDA) receptor coupled with intracellular calcium-signaling cascade is involved in the striatal ischemic injury and its remote effects on the target nuclei. Also, an intraventricular infusion of GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the striatal ischemic lesion. Furthermore, we have established an organotypic culture technique for the striatal tissue and then reproduced the NMDA-neurotoxicity on the striatal neurons in vitro which was not blocked by an activation of GABA_A receptor. In addition, overexpression of striatal enriched protein tyrosine phosphatase (STEP) was found to promote neuronal differentiation induced by a cAMP analogue in PC12 cells, suggesting that STEP may participate in neuronai modeling and/or plasticity. Therefore, we have a plan to elucidate whether a cell line changes its vulnerability to ischemic/anoxic insult by the STEP gene transfection.
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