PMID- 25926772
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150430
LR  - 20220129
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 9
DP  - 2015
TI  - Rapid modulation of synaptogenesis and spinogenesis by 17beta-estradiol in primary 
      cortical neurons.
PG  - 137
LID - 10.3389/fncel.2015.00137 [doi]
LID - 137
AB  - In the mammalian forebrain, the majority of excitatory synapses occur on 
      dendritic spines. Changes in the number of these structures is important for 
      brain development, plasticity and the refinement of neuronal circuits. The 
      formation of excitatory synapses involves the coordinated formation of dendritic 
      spines and targeting of multi-protein complexes to nascent connections. Recent 
      studies have demonstrated that the estrogen 17beta-estradiol (E2) can rapidly 
      increase the number of dendritic spines, an effect consistent with the ability of 
      E2 to rapidly influence cognitive function. However, the molecular composition of 
      E2-induced spines and whether these protrusions form synaptic connections has not 
      been fully elucidated. Moreover, which estrogen receptor(s) (ER) mediate these 
      spine-morphogenic responses are not clear. Here, we report that acute E2 
      treatment results in the recruitment of postsynaptic density protein 95 (PSD-95) 
      to novel dendritic spines. In addition neuroligin 1 (Nlg-1) and the NMDA receptor 
      subunit GluN1 are recruited to nascent synapses in cortical neurons. The presence 
      of these synaptic proteins at nascent synapses suggests that the machinery to 
      allow pre- and post-synapses to form connections are present in E2-induced 
      spines. We further demonstrate that E2 treatment results in the rapid and 
      transient activation of extracellular signal-regulated kinase 1/2 (ERK1/2), Akt 
      and the mammalian target of rapamycin (mTOR) signaling pathways. However, only 
      ERK1/2 and Akt are required for E2-mediated spinogenesis. Using synthetic 
      receptor modulators, we further demonstrate that activation of the estrogen 
      receptor beta (ERbeta) but not alpha (ERalpha) mimics rapid E2-induced spinogenesis and 
      synaptogenesis. Taken together these findings suggest that in primary cortical 
      neurons, E2 signaling via ERbeta, but not through ERalpha, is capable of remodeling 
      neuronal circuits by increasing the number of excitatory synapses.
FAU - Sellers, Katherine J
AU  - Sellers KJ
AD  - Department of Basic and Clinical Neuroscience, Institute of Psychiatry, 
      Psychology and Neuroscience, King's College London London, UK.
FAU - Erli, Filippo
AU  - Erli F
AD  - Department of Basic and Clinical Neuroscience, Institute of Psychiatry, 
      Psychology and Neuroscience, King's College London London, UK ; Department of 
      Biotechnology and Biosciences, Univeristy of Milano-Bicocca Milano, Italy.
FAU - Raval, Pooja
AU  - Raval P
AD  - Department of Basic and Clinical Neuroscience, Institute of Psychiatry, 
      Psychology and Neuroscience, King's College London London, UK.
FAU - Watson, Iain A
AU  - Watson IA
AD  - Department of Basic and Clinical Neuroscience, Institute of Psychiatry, 
      Psychology and Neuroscience, King's College London London, UK.
FAU - Chen, Ding
AU  - Chen D
AD  - Department of Basic and Clinical Neuroscience, Institute of Psychiatry, 
      Psychology and Neuroscience, King's College London London, UK.
FAU - Srivastava, Deepak P
AU  - Srivastava DP
AD  - Department of Basic and Clinical Neuroscience, Institute of Psychiatry, 
      Psychology and Neuroscience, King's College London London, UK.
LA  - eng
GR  - MR/L021064/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20150414
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC4396386
OTO - NOTNLM
OT  - 17beta-estradiol
OT  - Akt
OT  - ERK1/2
OT  - PSD-95
OT  - dendritic spines
OT  - estrogen receptor
OT  - mTOR
OT  - neuroligin-1
EDAT- 2015/05/01 06:00
MHDA- 2015/05/01 06:01
PMCR- 2015/01/01
CRDT- 2015/05/01 06:00
PHST- 2014/12/23 00:00 [received]
PHST- 2015/03/23 00:00 [accepted]
PHST- 2015/05/01 06:00 [entrez]
PHST- 2015/05/01 06:00 [pubmed]
PHST- 2015/05/01 06:01 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2015.00137 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2015 Apr 14;9:137. doi: 10.3389/fncel.2015.00137. 
      eCollection 2015.