PMID- 25892506
OWN - NLM
STAT- MEDLINE
DCOM- 20160324
LR  - 20191126
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 95
DP  - 2015 Aug
TI  - Neuroprotection in Parkinsonian-treated mice via estrogen receptor alpha activation 
      requires G protein-coupled estrogen receptor 1.
PG  - 343-52
LID - S0028-3908(15)00135-5 [pii]
LID - 10.1016/j.neuropharm.2015.04.006 [doi]
AB  - We have previously shown that estrogen receptors (ER) alpha activation and G 
      protein-coupled estrogen receptor 1 (GPER1) stimulation reproduce 17beta-estradiol 
      protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced toxicity 
      of dopamine neurons in mice. This suggests that both ERalpha and GPER1 have a major 
      role in mediating protection of dopamine neurons, but also suggests a potential 
      collaboration between these receptors. The present study tested the hypothesis of 
      a potential collaboration between ER alpha/beta and GPER1 in neuroprotection of 
      dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated male 
      mice, using a pharmacologic approach. The ERalpha/beta antagonist, ICI 182,780, blocked 
      the protective effects of 17beta-estradiol, but not those of GPER1 agonist G1, on 
      dopamine concentration as well as dopamine transporter and vesicular monoamine 
      transporter 2 specific binding in both the striatum and the substantia nigra. G1 
      protection was accompanied by an increase in Blc-2 and brain-derived neurotrophic 
      factor (BDNF) levels in the striatum; coadministration of ICI 182,780 blocked the 
      effect of G1 only on BDNF levels. ERalpha activation by its agonist 
      4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) protected dopamine 
      neurons, an effect associated with activation of striatal Akt signaling and an 
      increase in Bcl-2 and BDNF levels; the GPER1 antagonist G15 inhibited the 
      decrease in glycogen synthase kinase 3beta activity and the increase in BDNF induced 
      by PPT. Our results suggest that ERalpha requires GPER1 in protection of dopamine 
      neurons and modulation of signaling pathways, and that the effect of GPER1 occurs 
      independently of ERalpha/beta, whereas GPER1 require ERalpha/beta to increase BDNF levels.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Bourque, Melanie
AU  - Bourque M
AD  - Neuroscience Research Unit, Centre Hospitalier Universitaire de Quebec, CHUL, 
      Quebec City, Quebec, G1V 4G2, Canada; Faculty of Pharmacy, Laval University, 
      Quebec City, Quebec, G1K 7P4, Canada.
FAU - Morissette, Marc
AU  - Morissette M
AD  - Neuroscience Research Unit, Centre Hospitalier Universitaire de Quebec, CHUL, 
      Quebec City, Quebec, G1V 4G2, Canada.
FAU - Di Paolo, Therese
AU  - Di Paolo T
AD  - Neuroscience Research Unit, Centre Hospitalier Universitaire de Quebec, CHUL, 
      Quebec City, Quebec, G1V 4G2, Canada; Faculty of Pharmacy, Laval University, 
      Quebec City, Quebec, G1K 7P4, Canada. Electronic address: 
      therese.dipaolo@crchul.ulaval.ca.
LA  - eng
GR  - MOP-82692/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150417
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Estrogen Receptor Antagonists)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Estrogens)
RN  - 0 (GPER1 protein, mouse)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Steroids)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Antiparkinson Agents/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Corpus Striatum/drug effects/metabolism
MH  - Dopamine/metabolism
MH  - Estradiol/analogs & derivatives/pharmacology
MH  - Estrogen Receptor Antagonists/pharmacology
MH  - Estrogen Receptor alpha/*agonists/antagonists & inhibitors/metabolism
MH  - Estrogen Receptor beta/agonists/antagonists & inhibitors/metabolism
MH  - Estrogens/blood/pharmacology
MH  - Fulvestrant
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*pharmacology
MH  - Parkinsonian Disorders/*drug therapy/*metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Receptors, G-Protein-Coupled/*agonists/metabolism
MH  - Steroids/blood
OTO - NOTNLM
OT  - 17beta-Estradiol
OT  - Akt
OT  - Estrogen receptor
OT  - GPER1
OT  - MPTP
OT  - Neuroprotection
EDAT- 2015/04/22 06:00
MHDA- 2016/03/25 06:00
CRDT- 2015/04/21 06:00
PHST- 2014/12/30 00:00 [received]
PHST- 2015/03/16 00:00 [revised]
PHST- 2015/04/07 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/03/25 06:00 [medline]
AID - S0028-3908(15)00135-5 [pii]
AID - 10.1016/j.neuropharm.2015.04.006 [doi]
PST - ppublish
SO  - Neuropharmacology. 2015 Aug;95:343-52. doi: 10.1016/j.neuropharm.2015.04.006. 
      Epub 2015 Apr 17.