| Project/Area Number |
14380311
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KAWATO Suguru The University of Tokyo, Graduate School of Arts and Science, Professor, 大学院・総合文化研究科, 教授 (50169736)
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| Co-Investigator(Kenkyū-buntansha) |
KIMOTO Tetsuya The University of Tokyo, Graduate School of Arts and Science, Research Associate, 大学院・総合文化研究科, 助手 (60292843)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2002: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | neurosteroid / estradiol / hippocampus / learning and memory / long-term potentiation / estrogen receptor / cytochrome P450 / synapse / 記憶学習 / 神経成長 / シラプス / スパイン / 長期抑圧 / 膜上エストロジェン受容体 / 電気生理 |
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| Research Abstract |
In the present study, the synthesis of sex steroids, including dehydroepiandrosterone (DHEA), testosterone and 17β-estradiol, has been demonstrated in the adult rat hippocampus by metabolite analysis. The main path for the conversion from DHEA to testosterone in the hippocampus was shown to be 'DHEA→androstenediol→testosterone', which was different from the case in testis (DHEA→androstenedione→testosterone). With immunoelectron microscopy, the localization of essential enzymes for estrogen synthesis, cytochromes P45O17α and P450 aromatase, was demonstrated on membranous structures within spines of principal-neurons at hippocampal CA1 region. The localization of estrogen receptor a in the same structure was also demonstrated. Taken together, it seems to be plausible that estradiol plays a neuromodulative effect in the spine in which it was synthesized or in the spines located in adjacent places via membrane estrogen receptor α.
Furthermore, 2-hour treatment of hippocampal slices with estradiol was observed to induce the growth of spine length and the increase of the spine density in CA1 region. Estradiol might exert its effect on neuronal signal transmission via this neurogrowth factor-like action.
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