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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Pasqualini, Jorge R.

Editorial Board Member: Fujimoto, Jiro / Groner, Bernd / Hubalek, Michael / Morfin, Robert / Saad, Farid / Schally, Andrew V. / Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Campagnoli, Carlo / Carruba, Giuseppe / Chen, Shiuan / Chetrite, Gerard / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Danza, Giovanna / Darbre, Philippa D. / Daxenbichler, Günter / Kloet, Ronald / Nicola, Alejandro F. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Flores-Morales, Amilcar / Garcia-Segura, Luis M. / Gee, J.M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Hilakivi-Clarke, Leena / Hampl, Richard / Iwase, Hirotaka / Jordan, V.Craig / Klocker, Helmut / Kurebayashi, Jyunichi / Labrie, Fernand / Luu-The, Van / Mendelson, Carole R. / Mück, Alfred O. / Nicholson, Robert / Norman, Anthony W. / O'Malley, Bert W. / Rafestin-Oblin, Marie-Edith / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Sanchez, Edwin R. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Verhoeven, Guido / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Ylikomi, Timo / Yu, Qi

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Regulation of synaptic plasticity by hippocampus synthesized estradiol

Anna M. Barron1 / Yasushi Hojo1–3, , / Hideo Mukai1–3, , / Shimpei Higo1 / Yuuki Ooishi1 / Yusuke Hatanaka1 / Mari Ogiue-Ikeda1, 4 / Gen Murakami1, 3 / Tetsuya Kimoto1–3, , / 1–4, , ,

1Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan

2Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, The University of Tokyo, Tokyo, Japan

3Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo, Tokyo, Japan

4Project of Special Coordinate Funds for Promoting Science and Technology, The University of Tokyo, Tokyo, Japan

Corresponding author: Dr. Suguru Kawato, Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo, 153-8902, Japan Phone/Fax: +81 3 5454 6517

Citation Information: Hormone Molecular Biology and Clinical Investigation. Volume 7, Issue 2, Pages 361–375, ISSN (Online) 1868-1891, ISSN (Print) 1868-1883, DOI: 10.1515/HMBCI.2011.118, August 2011

Publication History

Received:
2011-06-17
Accepted:
2011-07-21
Published Online:
2011-08-29

Abstract

Estradiol is synthesized from cholesterol in hippocampal neurons of adult rats by cytochrome P450 and hydroxysteroid dehydrogenase enzymes. These enzymes are expressed in the glutamatergic neurons of the hippocampus. Surprisingly, the concentration of estradiol and androgen in the hippocampus is significantly higher than that in circulation. Locally synthesized estradiol rapidly and potently modulates synaptic plasticity within the hippocampus. E2 rapidly potentiates long-term depression and induces spinogenesis through synaptic estrogen receptors and kinases. The rapid effects of estradiol are followed by slow genomic effects mediated by both estrogen receptors located at the synapse and nucleus, modulating long-term potentiation and promoting the formation of new functional synaptic contacts. Age-related changes in hippocampally derived estradiol synthesis and distribution of estrogen receptors may alter synaptic plasticity, and could potentially contribute to age-related cognitive decline. Understanding factors which regulate hippocampal estradiol synthesis could lead to the identification of alternatives to conventional hormone therapy to protect against age-related cognitive decline.

Keywords: aging; estradiol; estrogen receptor; hippocampus; hormone therapy; long-term depression; long-term potentiation; neurosteroid; selective estrogen receptor modulator; spine; synaptic plasticity

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