Grant-in-Aid for international Scientific Research
|Allocation Type||Single-year Grants|
|Research Institution||University of the Air|
KITO Shozo University of the Air, Liberal Arts, Professor, 教養学部, 教授 (00010140)
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
MAGGI A. Ins. of Pharmacolgy Sci., Univ. of Milan, Associate
BARNARD E. A Royal Free Hosp. Sch. of Medicine, Professor
JOH Tong H Cornell University Medical College, Professor
BARNARD Elic Royal Free Hospital School of Medicine, Professor
JOH Tong H. Cornell University Medical College, Professor
|Project Period (FY)
1995 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥6,600,000 (Direct Cost : ¥6,600,000)
Fiscal Year 1996 : ¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1995 : ¥3,300,000 (Direct Cost : ¥3,300,000)
|Keywords||Estrogen / Hepatocyto growth factor / Insulin-like growth factor / Gel shift assay / Neuronal growth factor / Kainic acid / Neuronal plasticity / AP-1-DNA binding activity / LDH effluxmetry / 神経細胞栄養因子 / Estrogen受容体|
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.