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Activation of estrogen receptor-b regulates hippocampal synaptic plasticity and improves memory

Summary: Activation of estrogen receptor-b regulates
hippocampal synaptic plasticity and improves memory
Feng Liu1,6, Mark Day2,6, Luis C Mun~iz1, Daniel Bitran3, Robert Arias1, Raquel Revilla-Sanchez4, Steve Grauer1,
Guoming Zhang1, Cody Kelley1, Virginia Pulito1, Amy Sung1, Ronald F Mervis5, Rachel Navarra1,
Warren D Hirst1, Peter H Reinhart1, Karen L Marquis1, Stephen J Moss4, Menelas N Pangalos1 &
Nicholas J Brandon1
Estrogens have long been implicated in influencing cognitive processes, yet the molecular mechanisms underlying these effects
and the roles of the estrogen receptors alpha (ERa) and beta (ERb) remain unclear. Using pharmacological, biochemical and
behavioral techniques, we demonstrate that the effects of estrogen on hippocampal synaptic plasticity and memory are mediated
through ERb. Selective ERb agonists increased key synaptic proteins in vivo, including PSD-95, synaptophysin and the AMPA-
receptor subunit GluR1. These effects were absent in ERb knockout mice. In hippocampal slices, ERb activation enhanced long-
term potentiation, an effect that was absent in slices from ERb knockout mice. ERb activation induced morphological changes in
hippocampal neurons in vivo, including increased dendritic branching and increased density of mushroom-type spines. An ERb
agonist, but not an ERa agonist, also improved performance in hippocampus-dependent memory tasks. Our data suggest that
activation of ERb can regulate hippocampal synaptic plasticity and improve hippocampus-dependent cognition.
There are two well characterized estrogen receptors, ERa and ERb,
described in mammals1,2. They both function as nuclear transcription
factors modulating expression of their target genes in response to
changes in estrogen levels. ERa and ERb share similar domain
organization and show substantial sequence homology but have


Source: Alford, Simon - Department of Biological Sciences, University of Illinois at Chicago


Collections: Biology and Medicine