Research article summary (published 12 Oct 2009):

Cytoskeletal changes underlie estrogen's acute effects on synaptic transmission and plasticity.

Full 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.

Author information

Author/s: Kramár, Enikö A (EA); Chen, Lulu Y (LY); Brandon, Nicholas J (NJ); Rex, Christopher S (CS); Liu, Feng (F); Gall, Christine M (CM); Lynch, Gary (G);

Affiliation: Department of Psychiatry, University of California, Irvine, California 92697, USA.

Grants: MH083396 (Agency:NIMH NIH HHS) ; NS045260 (Agency:NINDS NIH HHS) ; NS045540 (Agency:NINDS NIH HHS) ; NS051923 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 41) : pp 12982-93

Dates: Created 2009/10/15; Completed 2009/10/30;

PMID: 19828812, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Actins - metabolism Age Factors Analysis of Variance Animals Animals, Newborn Bicyclo Compounds, Heterocyclic - pharmacology Biophysics Cytoskeleton - metabolism Dendritic Spines - drug effects; physiology Dose-Response Relationship, Drug Electric Stimulation - methods Estradiol - analogs & derivatives; pharmacology Estrogen Antagonists - pharmacology Estrogens - metabolism Excitatory Amino Acid Antagonists - pharmacology Excitatory Postsynaptic Potentials - drug effects; physiology Female GABA Antagonists - pharmacology Ginsenosides - pharmacology

Hippocampus - cytology Long-Term Potentiation - drug effects Male Microscopy, Confocal Neural Pathways - physiology Neuronal Plasticity - drug effects; physiology Neurons - cytology; drug effects; physiology Ovariectomy - methods Oxazoles - pharmacology Patch-Clamp Techniques - methods Phenols - pharmacology Picrotoxin - pharmacology Rats Rats, Long-Evans Rats, Sprague-Dawley Sapogenins - pharmacology Signal Transduction - drug effects Synaptic Transmission - drug effects; physiology Thiazolidines - pharmacology

Associated Chemicals: Actins (0) ; Bicyclo Compounds, Heterocyclic (0) ; Estrogen Antagonists (0) ; Estrogens (0) ; Excitatory Amino Acid Antagonists (0) ; GABA Antagonists (0) ; Ginsenosides (0) ; Oxazoles (0) ; Phenols (0) ; Sapogenins (0) ; Thiazolidines (0) ; WAY 200070 (0) ; ginsenoside 20S-protopanaxatriol (0) ; Picrotoxin (124-87-8) ; fulvestrant (129453-61-8) ; Estradiol (50-28-2) ; latrunculin A (76343-93-6)

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