Project/Area Number |
07457125
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
内科学一般
|
Research Institution | University of the Air |
Principal Investigator |
KITO Shozo University of the Air, Liberal Arts, Professor, 教養学部, 教授 (00010140)
|
Co-Investigator(Kenkyū-buntansha) |
SEMBA Jun'ichi Univ.of the Air, Liberal Arts, Associate Professor, 教養学部, 助教授 (30183429)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1995: ¥4,200,000 (Direct Cost: ¥4,200,000)
|
Keywords | estrogen / kainic acid / AP-1-DNA binding activity / CA^<2+> / insulin-like growth factor / Immunohistochemistry / dot blotting / in situ hybridization / 海馬 / ジヒドロピリジン系Ca拮抗薬 / hepatocyte growth factor / mRNA |
Research Abstract |
Estrogen is deeply associated not only with development and differentiational of neuronal cells, but also with rescue mechanisms of injured or aging neurons. Our foregoing studies revealed that estrogen caused increase of the survival rate of rat hippocampal culture neurons at concentrations of 10^<-6>-10^<-9>, while depressed the survival at higher concetrations. Basing on these results, mechanisms of neuroprotective effects of estrogen were studied on kainic acid-injured brains. Immunohistochemical studies with use of monoclonal antibody against estrogen receptor showed marked increase of estrogen receptor-like immunoreactivities not only in the limbic system, but also in the wide areas of the cerebral cortesses. Such results were also confirmed through in situ hybridization experiments for estrogen receptor mRNA.Estrogen injection prior to a systemic administration of kainic acid-induced expression of neurotrophic factor and their mRNAs such as HGF,IGF I and II,as observed by dot blotting analysis, immunohistochemistry as well as in situ hybridization. Through a separate experiment with single injection of estrogen, we confirmed that estrogen increased AP-1-DNA binding activity with time course up to 120 min. when observed by gel shift assay method. These results suggested that estrogen playd roles in neuronal repair with successive proceses of increased estrogen receptors, elevation of AP-1-DNA binding activity, induction of IGF I mRNA.Neuronally differentiated PC12 cells by NGF have estrogen receptors. We noticed estrogen lenpthened the survival of PC12 cells when added together with NGF.
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