title: Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons.
abstract: Rapid modulation of hippocampal synaptic plasticity by estrogen has long been a hot topic, but analysis of molecular mechanisms via synaptic estrogen receptors has been seriously difficult. Here, two types of independent synaptic plasticity, long-term depression (LTD) and spinogenesis, were investigated, in response to 17beta-estradiol and agonists of estrogen receptors using hippocampal slices from adult male rats. Multi-electrode investigations demonstrated that estradiol rapidly enhanced LTD not only in CA1 but also in CA3 and dentate gyrus. Dendritic spine morphology analysis demonstrated that the density of thin type spines was selectively increased in CA1 pyramidal neurons within 2 h after application of 1 nm estradiol. This enhancement of spinogenesis was completely suppressed by mitogen-activated protein (MAP) kinase inhibitor. Only the estrogen receptor (ER) alpha agonist, (propyl-pyrazole-trinyl)tris-phenol (PPT), induced the same enhancing effect as estradiol on both LTD and spinogenesis in the CA1. The ERbeta agonist, (4-hydroxyphenyl)-propionitrile (DPN), suppressed LTD and did not affect spinogenesis. Because the mode of synaptic modulations by estradiol was mostly the same as that by the ERalpha agonist, a search was made for synaptic ERalpha using purified RC-19 antibody qualified using ERalpha knockout (KO) mice. Localization of ERalpha in spines of principal glutamatergic neurons was demonstrated using immunogold electron microscopy and immunohistochemistry. ERalpha was also located in nuclei, cytoplasm and presynapses.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Mukai
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Tsurugizawa
authors.forename: Gen
authors.initials: G
authors.lastname: Murakami
authors.forename: Shiro
authors.initials: S
authors.lastname: Kominami
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishii
authors.forename: Mari
authors.initials: M
authors.lastname: Ogiue-Ikeda
authors.forename: Norio
authors.initials: N
authors.lastname: Takata
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanabe
authors.forename: Aizo
authors.initials: A
authors.lastname: Furukawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Ooishi
authors.forename: John H
authors.initials: JH
authors.lastname: Morrison
authors.forename: William G M
authors.initials: WG
authors.lastname: Janssen
authors.forename: John A
authors.initials: JA
authors.lastname: Rose
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Izumi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D016253:Microscopy, Immunoelectron / Q000379:methods; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D010636:Phenols; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000172:deficiency / Q000502:physiology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D018691:Excitatory Amino Acid Antagonists; D010636:Phenols; D011720:Pyrazoles; D011960:Receptors, Estrogen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D000077267:Fulvestrant; D004958:Estradiol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione