title: Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks.
abstract: This article is part of a Special Issue "Estradiol and cognition". Estradiol (E2) is locally synthesized within the hippocampus and the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. The molecular mechanisms of modulation through the synaptic estrogen receptor (ER) and its downstream signaling, however, are largely unknown in the dentate gyrus (DG). We investigated the E2-induced modulation of dendritic spines in male adult rat hippocampal slices by imaging Lucifer Yellow-injected DG granule cells. Treatments with 1 nM E2 increased the density of spines by approximately 1.4-fold within 2h. Spine head diameter analysis showed that the density of middle-head spines (0.4-0.5 μm) was significantly increased. The E2-induced spine density increase was suppressed by blocking Erk MAPK, PKA, PKC and LIMK. These suppressive effects by kinase inhibitors are not non-specific ones because the GSK-3β antagonist did not inhibit E2-induced spine increase. The ER antagonist ICI 182,780 also blocked the E2-induced spine increase. Taken together, these results suggest that E2 rapidly increases the density of spines through kinase networks that are driven by synaptic ER.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan; Bioinformatics Project of Japan Science and Technology Agency, University of Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Munetomo
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan; Bioinformatics Project of Japan Science and Technology Agency, University of Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Mukai
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
authors.forename: Muneki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Sato
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan; Bioinformatics Project of Japan Science and Technology Agency, University of Tokyo, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Murakami
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Komatsuzaki
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan; Bioinformatics Project of Japan Science and Technology Agency, University of Tokyo, Japan; Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo 113-8431, Japan. Electronic address: kawato@bio.c.u-tokyo.ac.jp.
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: D000818:Animals; D002452:Cell Count; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D065171:Estrogen Receptor Antagonists; D000077267:Fulvestrant; D004958:Estradiol; D011494:Protein Kinases
keywords: 17β-Estradiol; Dentate gyrus; Estrogen receptor; Hippocampus; Spine; Spinogenesis; Synapse