Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons.
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.
Mukai
Hideo
H
Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro, Tokyo, Japan.
Tsurugizawa
Tomokazu
T
Murakami
Gen
G
Kominami
Shiro
S
Ishii
Hirotaka
H
Ogiue-Ikeda
Mari
M
Takata
Norio
N
Tanabe
Nobuaki
N
Furukawa
Aizo
A
Hojo
Yasushi
Y
Ooishi
Yuuki
Y
Morrison
John H
JH
Janssen
William G M
WG
Rose
John A
JA
Chambon
Pierre
P
Kato
Shigeaki
S
Izumi
Shunsuke
S
Yamazaki
Takeshi
T
Kimoto
Tetsuya
T
Kawato
Suguru
S
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
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