| Co-Investigator(Kenkyū-buntansha) |
MAGGI A Univ.of Milan, Ins.of Pharmacology Sci., Associate Professor, Univ. of Milano, Associate
BARNARD E.A Royal Free Hosp., Sch.of Medicine, Professor, Professor
JHO Tong H Cornell University Medical College, Professor
MIYOSHI Rie Royal Free Hosp., Sch.of Medicine, Research Associate, Research A (80209965)
SEMBA Jun'ichi Univ.of the Air, Liberal Arts, Associate Professor, 教養学部, 助教授 (30183429)
NOMURA Yasuyuki Hokkaido Univ., sch.of Pharmacol., Professor, 薬学部, 教授 (00034041)
TOHYAMA Masaya Osaka Univ., Sch.of Medicine, Professor, 医学部, 教授 (40028593)
OLSEN Richard W UCLA,Sch.of Medicine, Professor, Professor
H.JOH Tong Cornell Univ., Medical College, Professor
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| Research Abstract |
Our foregoing studies revealed that estrogen caused increase of the survival rate of rat hippocampal culture neurons at lower concentrations, contrary to the case of glucocorticoid. Basing on this result, 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. Estrogen injection prior to kainic acid also increased GAP43 like immunoreactities in the hippocampus.
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 neuronl repair with successive processes of increased estrogen receptors, elevation of AP-1-DNA binding activity, induction of IGF I mRNA AND GAP43 expression.
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