Cytoskeletal changes underlie estrogen's acute effects on synaptic transmission and plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] Journal article

Title	Cytoskeletal changes underlie estrogen's acute effects on synaptic transmission and plasticity.
Author(s)	Kramár EA, Chen LY, Brandon NJ, Rex CS, Liu F, Gall CM, Lynch G
Institution	Department of Psychiatry, University of California, Irvine, California 92697, USA.
Source	J Neurosci 2009 Oct 14; 29(41):12982-93.
MeSH	Actins Age Factors Analysis of Variance Animals Animals, Newborn Bicyclo Compounds, Heterocyclic Biophysics Cytoskeleton Dendritic Spines Dose-Response Relationship, Drug Electric Stimulation Estradiol Estrogen Antagonists Estrogens Excitatory Amino Acid Antagonists Excitatory Postsynaptic Potentials Female GABA Antagonists Ginsenosides Hippocampus Long-Term Potentiation Male Microscopy, Confocal Neural Pathways Neuronal Plasticity Neurons Ovariectomy Oxazoles Patch-Clamp Techniques Phenols Picrotoxin Rats Rats, Long-Evans Rats, Sprague-Dawley Sapogenins Signal Transduction Synaptic Transmission Thiazolidines
Abstract	Estrogen, in addition to its genomic effects in brain, causes rapid and reversible changes to synaptic operations. We report here that these acute actions are due to selective activation of an actin-signaling cascade normally used in the production of long-term potentiation (LTP). Estrogen, or a selective agonist of the steroid's beta-receptor, caused a modest increase in fast glutamatergic transmission and a pronounced facilitation of LTP in adult hippocampal slices; both effects were completely eliminated by latrunculin, a toxin that prevents actin filament assembly. Estrogen also increased spine concentrations of filamentous actin and strongly enhanced its polymerization in association with LTP. A search for the origins of these effects showed that estrogen activates the small GTPase RhoA and phosphorylates (inactivates) the actin severing protein cofilin, a downstream target of RhoA. Moreover, an antagonist of RhoA kinase (ROCK) blocked estrogen's synaptic effects. Estrogen thus emerges as a positive modulator of a RhoA>ROCK>LIM kinase>cofilin pathway that regulates the subsynaptic cytoskeleton. It does not, however, strongly affect a second LTP-related pathway, involving the GTPases Rac and Cdc42 and their effector p21-activated kinase, which may explain why its acute effects are reversible. Finally, ovariectomy depressed RhoA activity, spine cytoskeletal plasticity, and LTP, whereas brief infusions of estrogen rescued plasticity, suggesting that the deficits in plasticity arise from acute, as well as genomic, consequences of hormone loss.
Language	eng
Pub Type(s)	In Vitro Journal Article Research Support, N.I.H., Extramural
PubMed ID	19828812

Advertise on this site.