1. Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation.
- Author
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Spencer-Segal JL, Tsuda MC, Mattei L, Waters EM, Romeo RD, Milner TA, McEwen BS, and Ogawa S
- Subjects
- Animals, Brain-Derived Neurotrophic Factor biosynthesis, Brain-Derived Neurotrophic Factor genetics, Data Interpretation, Statistical, Densitometry, Disks Large Homolog 4 Protein, Estrogen Receptor alpha genetics, Estrogen Receptor beta genetics, Estrous Cycle drug effects, Estrous Cycle physiology, Female, Guanylate Kinases metabolism, Hippocampus cytology, Hormone Replacement Therapy, Immunohistochemistry, In Situ Hybridization, Membrane Proteins metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Ovariectomy, Proto-Oncogene Proteins c-akt metabolism, Receptor, trkB biosynthesis, Receptor, trkB genetics, Estradiol pharmacology, Estrogen Receptor alpha drug effects, Estrogen Receptor beta drug effects, Hippocampus drug effects, Neural Pathways drug effects, Neuronal Plasticity drug effects, Synapses drug effects
- Abstract
Estradiol affects hippocampal-dependent spatial memory and underlying structural and electrical synaptic plasticity in female mice and rats. Using estrogen receptor (ER) alpha and beta knockout mice and wild-type littermates, we investigated the role of ERs in estradiol effects on multiple pathways important for hippocampal plasticity and learning. Six hours of estradiol administration increased immunoreactivity for phosphorylated Akt throughout the hippocampal formation, whereas 48 h of estradiol increased immunoreactivity for phosphorylated TrkB receptor. Estradiol effects on phosphorylated Akt and TrkB immunoreactivities were abolished in ER alpha and ER beta knockout mice. Estradiol also had distinct effects on immunoreactivity for post-synaptic density 95 (PSD-95) and brain derived-neurotrophic factor (BDNF) mRNA in ER alpha and beta knockout mice. Thus, estradiol acts through both ERs alpha and beta in several subregions of the hippocampal formation. The different effects of estradiol at 6 and 48 h indicate that several mechanisms of estrogen receptor signaling contribute to this female hormone's influence on hippocampal synaptic plasticity. By further delineating these mechanisms, we will better understand and predict the effects of endogenous and exogenous ovarian steroids on mood, cognition, and other hippocampal-dependent behaviors., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2012
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