| Project/Area Number |
04044143
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | The University of the Air |
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Principal Investigator |
KITO Shozo Div.of Health Sciences, the University of the Air, Professor, 教養学部, 教授 (00010140)
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| Co-Investigator(Kenkyū-buntansha) |
MAGGI A. Ins.of Pharmacology Science, University of Milano, Associate Professor, University o, Associate
MIYOSHI Rie Royal Free Hospital School of Medicine, London, Research Asscoiate, Research A (80209965)
SEMBA Jun'ichi Div.of Health Sciences, University of the Air Associate Professor, 教養学部, 助教授 (30183429)
BARNARD Elic.a. Royal Free Hospital School of Medicine, London, Professor, Professor
JOH Tong h. Cornell University Medical College, Professor, Professor
TOHYAMA Masaya Institute of Medicine, Osaka University, Professor, 医学部, 教授 (40028593)
OLSEN Richard w. UCLA School of Medicine, Professor, Professor
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| Project Period (FY) |
1992 – 1994
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| Keywords | estrogen / immediate early gene / glucocortitoid / c-fos / Ca^<2+> / hepatocyte growth factor / nothern blotting / kainic acid |
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| Research Abstract |
As a part of the study on how biologically active substances in the brain cause long-term effects through immediate early genes, effects of steroid hormones on survival rate of cultured rat limbic neurons were investigated.
It was previously confirmed that in cultured limbic neurons glucocorticoid increased kainic acid-induced cytotoxicity dose-dependently, while estrogen increased survival rate of cultured neurons at concentrations lower than 10^<-6>M.To elucidate this effect of estrogen, in situ hybridization of c-fos was performed on the rat limbic system after general administration of estrogen.
As the results, we confirmed that estrogen induced c-fos activation, while glucocorticoid administration did not. It has been known that glucocorticoid inhibits AP-1 site. These results suggested that estrogen and glucocorticoid reciprocally regulated immediate early genes. Such effect of estrogen is probably related with our experimental data that estrogen sometimes causes long-term elevation of Ca^<2+> within cultured hippocampal neurons.
Our hypothesis is that the next targent gene to the immediate early gene may be hepatocyte growth factor (HGF) gene since HGF is related with repairing also nervous tissue after injury and glucocorticoid inhibits HGF mRNA activation. Northern blotting analysis of HGF and c-met mRNA was performed on the rat hippocampus after general administration of kainic acid. HGF and c-met mRNA were induced 6 to 48 hours after kainic acid injection. Effect of steroid hormones on this kainic acid-induced HGF mRNA was under progress.
To confirm the effect of estrogen on neurons more precisely, neuroblastoma cell line into which estrogen receptor gene was transfected was used. By adding estrogen to this cell line, the neuroblastoma cells differentiated into matured neurons. We are experimenting the effect of estrogen on neurons using this cell line differentiated by estrogen.
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