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Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons
Mukai H., Tsurugizawa T.,
Murakami G., Kominami S., Ishii H., Ogiue-Ikeda M., Takata N.,
Tanabe N., Fukukawa A., Hojo Y., Ooishi Y., Morrison J.H., Janssen W.G.M., Rose J.A. Chambon
P., Kato S., Izumi S., Yamazaki T., Kimoto T. and Kawato
S.
J Neurochem. 2007 Feb;100(4):950-67
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.
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