What is it about?

Estradiol is known to produce greater numbers of dendritic spines in the brain. However, the types of spines and the molecules incorporated in these structures have been underexplored. Our study examines the rapid effects of estradiol on dendritic spines and the localization of synaptic molecules within these structures in the mammalian hippocampus. We find that 120 minutes after administration of estradiol, large mushroom-shaped spines are prevalent compared to 30 minutes and vehicle. Additionally, we find that the subunit of the excitatory AMPA receptor, GluA2, and its supporting scaffold protein, PSD-95, are found on these mushroom spines.

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Why is it important?

Our study reveals that estradiol can modulate synaptic plasticity in the hippocampus specifically by enhancing the density of mushroom spines. These specific structures are thought to be more mature than their smaller counterparts, as their increased surface area allows for greater synaptic efficacy. Indeed, our study also confirms that estradiol increases the availability of proteins, GluA2 and PSD95, which are pivotal to synaptic plasticity in these very dendritic structures. Our results offer mechanisms that underlie estradiol's effects on neural plasticity and can help us further understand the role of hormones in modulating synaptic plasticity and learning & memory.

Perspectives

There has been long-standing interest in estradiol's potential as a pharmacological tool to combat cognitive deficits observed in Alzheimer's Disease and other age-related dementias. However, clinical studies have shown inconsistent promise in that regard. Nonetheless, the neuroprotective properties of estrogens, and estradiol in particular, continue to pique interest in the field today. Studies on the rapid, direct structural and molecular effects of estradiol on the brain can offer new avenues to explore therapeutic strategies in various diseases associated with cognitive decline. Future work should explore how these rapid effects translate to cognitive function in animal models, to remediate cognitive deficits associated with aging and drug abuse, among others.

Jorge Avila
Hunter College City University of New York

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This page is a summary of: Estradiol rapidly increases GluA2-mushroom spines and decreases GluA2-filopodia spines in hippocampus CA1, Hippocampus, August 2017, Wiley,
DOI: 10.1002/hipo.22768.
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