title: Corticosterone rapidly increases thorns of CA3 neurons via synaptic/extranuclear glucocorticoid receptor in rat hippocampus.
abstract: Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500, and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100-1000 nM) might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo Tokyo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yoshiya
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Department of Physics, College of Science and Technology, Nihon University Chiyoda, Tokyo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Komatsuzaki
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo 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, The University of Tokyo Tokyo, Japan.
authors.forename: Muneki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo 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, The University of Tokyo Tokyo, Japan ; Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo Tokyo, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Murakami
authors.affiliation: Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine Kamigyo, Kyoto, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo Tokyo, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone
keywords: corticosterone; hippocampus; kinase; spine; stress; thorn