title: Estradiol rapidly rescues synaptic transmission from corticosterone-induced suppression via synaptic/extranuclear steroid receptors in the hippocampus.
abstract: We investigated rapid protection effect by estradiol on corticosterone (CORT)-induced suppression of synaptic transmission. Rapid suppression by 1 μM CORT of long-term potentiation (LTP) at CA3-CA1 synapses was abolished via coperfusion of 1 nM estradiol. N-methyl-D-aspartate (NMDA) receptor-derived field excitatory postsynaptic potential (NMDA-R-fEPSP) was used to analyze the mechanisms of these events. Estradiol abolished CORT-induced suppression of NMDA-R-fEPSP slope. This CORT-induced suppression was abolished by calcineurin inhibitor, and the rescue effect by estradiol on the CORT-induced suppression was inhibited by mitogen-activated protein (MAP) kinase inhibitor. The CORT-induced suppressions of LTP and NMDA-R-fEPSP slope were abolished by glucocorticoid receptor (GR) antagonist, and the restorative effects by estradiol on these processes were mimicked by estrogen receptor α (ERα) and ERβ agonists. Taken together, estradiol rapidly rescued LTP and NMDA-R-fEPSP slope from CORT-induced suppressions. A GR→calcineurin pathway is involved in these suppressive effects. The rescue effects by estradiol are driven via ERα or ERβ→MAP kinase pathway. Synaptic/extranuclear GR, ERα, and ERβ probably participate in these rapid events. Mass-spectrometric analysis determined that acute hippocampal slices used for electrophysiological measurements contained 0.48 nM estradiol less than exogenously applied 1 nM. In vivo physiological level of 8 nM estradiol could protect the intact hippocampus against acute stress-induced neural suppression.
authors: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.
authors: Yuuki
authors: Y
authors: Ooishi
authors: Hideo
authors: H
authors: Mukai
authors: Yasushi
authors: Y
authors: Hojo
authors: Gen
authors: G
authors: Murakami
authors: Yoshitaka
authors: Y
authors: Hasegawa
authors: Tomu
authors: T
authors: Shindo
authors: John H
authors: JH
authors: Morrison
authors: Tetsuya
authors: T
authors: Kimoto
authors: Suguru
authors: S
authors: Kawato
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001703:Biophysics; D003345:Corticosterone / Q000494:pharmacology; D004558:Electric Stimulation; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D016253:Microscopy, Immunoelectron; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011959:Receptors, Estradiol / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D004967:Estrogens; D018691:Excitatory Amino Acid Antagonists; D011959:Receptors, Estradiol; D013256:Steroids; D004958:Estradiol; D003345:Corticosterone