Activation of estrogen receptor-b regulates hippocampal synaptic plasticity and improves memory (Nat Neurosci, 2008, 11:334-343)

報告日期: 2008/12/19
報告時間: 16:00/16:50
報告學生: 洪惠琪
講評老師: 吳豐森

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

Nat Neurosci 11, 334-342, 2008

Feng Liu, Mark Day, Luis C Mun˜iz, Daniel Bitran, Robert Arias, Raquel Revilla-Sanchez, Steve Grauer, Guoming Zhang, Cody Kelley, Virginia Pulito, Amy Sung.


Speaker: Hung, Huei-Chi

Commentator: Wu, Fong-Sen

16:00-16:50, Dec 19, 2008, Room 602


17-b-estradiol, a main form of estrogen, has been reported to enhance learning and memory in rodent. It has been shown to promote the formation of new dendritic spines and excitatory synapses in the hippocampus, increase the expression of NMDA receptor subunit NR2B and enhance NMDAR-mediated synaptic activity and long-term potentiation (LTP). There are two well characterized estrogen receptors, ERa and ERb, described in mammals. They both function as nuclear transcription factors modulating expression of their target genes in response to changes in estrogen levels. Supporting this functional divergence, ERa and ERb have been shown to be differentially expressed throughout the rodent brain. ERa and ERb are both expressed in the hippocampus, a region of the brain involved in cognitive function. Within the hippocampus, ERb is expressed in the CA3 stratum lucidum, CA1 stratum radiatum and dentate gyrus regions and at the subcellular level is found in axons, dendrites and dendritic spines. The identity of the estrogen receptor responsible for mediating the effects of estrogen on cognition has not yet been fully resolved. The authors 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 LTP, 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. The author suggests that activation of ERb can regulate hippocampal synaptic plasticity and improve hippocampus-dependent cognition.



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