PMID- 23103216
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20211021
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 239
DP  - 2013 Jun 3
TI  - Estrogen promotes learning-related plasticity by modifying the synaptic 
      cytoskeleton.
PG  - 3-16
LID - S0306-4522(12)01053-6 [pii]
LID - 10.1016/j.neuroscience.2012.10.038 [doi]
AB  - Estrogen's acute, facilitatory effects on glutamatergic transmission and 
      long-term potentiation (LTP) provide a potential explanation for the steroid's 
      considerable influence on behavior. Recent work has identified mechanisms 
      underlying these synaptic actions. Brief infusion of 17ss-estradiol (E2) into 
      adult male rat hippocampal slices triggers actin polymerization within dendritic 
      spines via a signaling cascade beginning with the GTPase RhoA and ending with 
      inactivation of the filament-severing protein cofilin. Blocking this sequence, or 
      actin polymerization itself, eliminates E2's effects on synaptic physiology. 
      Notably, the theta burst stimulation used to induce LTP activates the same 
      signaling pathway as E2 plus events that stabilize the reorganization of the 
      sub-synaptic cytoskeleton. These observations suggest that E2 elicits a partial 
      form of LTP, resulting in an increase of fast excitatory postsynaptic potentials 
      (EPSPs) and a reduction in the threshold for lasting synaptic changes. While E2's 
      effects on the cytoskeleton could be direct, results described here indicate that 
      the hormone activates synaptic tropomyosin-related kinase B (TrkB) receptors for 
      brain-derived neurotrophic factor (BDNF), a releasable neurotrophin that 
      stimulates the RhoA to cofilin pathway. It is therefore possible that E2 acts via 
      transactivation of neighboring receptors to modify the composition and structure 
      of excitatory contacts. Finally, there is the question of whether a loss of acute 
      synaptic actions contributes to the memory problems associated with estrogen 
      depletion. Initial tests found that ovariectomy in middle-aged rats disrupts RhoA 
      signaling, actin polymerization, and LTP consolidation. Acute applications of E2 
      reversed these defects, a result consistent with the idea that disturbances to 
      actin management are one cause of behavioral effects that emerge with reductions 
      in steroid levels.
CI  - Copyright (c) 2013. Published by Elsevier Ltd.
FAU - Kramar, E A
AU  - Kramar EA
AD  - Department of Anatomy and Neurobiology, University of California, Irvine, CA 
      92697, USA. ekramar@uci.edu
FAU - Babayan, A H
AU  - Babayan AH
FAU - Gall, C M
AU  - Gall CM
FAU - Lynch, G
AU  - Lynch G
LA  - eng
GR  - R01 NS051823/NS/NINDS NIH HHS/United States
GR  - MH082042/MH/NIMH NIH HHS/United States
GR  - R01 MH082042/MH/NIMH NIH HHS/United States
GR  - NS045260/NS/NINDS NIH HHS/United States
GR  - P01 NS045260/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20121025
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Estrogens)
SB  - IM
MH  - Animals
MH  - Cytoskeleton/*metabolism
MH  - Estrogens/*metabolism
MH  - Humans
MH  - Learning/*physiology
MH  - Neuronal Plasticity/*physiology
MH  - Synapses/*metabolism
MH  - Synaptic Transmission/*physiology
PMC - PMC4472431
MID - NIHMS697014
EDAT- 2012/10/30 06:00
MHDA- 2013/10/18 06:00
PMCR- 2015/06/18
CRDT- 2012/10/30 06:00
PHST- 2012/08/01 00:00 [received]
PHST- 2012/10/11 00:00 [revised]
PHST- 2012/10/18 00:00 [accepted]
PHST- 2012/10/30 06:00 [entrez]
PHST- 2012/10/30 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2015/06/18 00:00 [pmc-release]
AID - S0306-4522(12)01053-6 [pii]
AID - 10.1016/j.neuroscience.2012.10.038 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Jun 3;239:3-16. doi: 10.1016/j.neuroscience.2012.10.038. Epub 
      2012 Oct 25.