Hormone Molecular Biology and Clinical Investigation
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Regulation of synaptic plasticity by hippocampus synthesized estradiol
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
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
- Published Online:
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