title: Regulation of synaptic plasticity by hippocampus synthesized estradiol.
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.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Barron
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.forename: Hideo
authors.initials: H
authors.lastname: Mukai
authors.forename: Shimpei
authors.initials: S
authors.lastname: Higo
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Ooishi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Mari
authors.initials: M
authors.lastname: Ogiue-Ikeda
authors.forename: Gen
authors.initials: G
authors.lastname: Murakami
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato