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PMID: 19596275 Published · ppublish English Journal Article

Estrogen receptor alpha and beta specific agonists regulate expression of synaptic proteins in rat hippocampus.

Brain research ·Vol. 1290 ·2009-09-22 ·Pages 1-11

Waters EM, Mitterling K, Spencer JL, Mazid S, McEwen BS, Milner TA

Abstract

Changes in hippocampal CA1 dendritic spine density and synaptic number across the estrous cycle in female rats correlate with increased hippocampal-dependent cognitive performance in a manner that is dependent on estrogen receptors (ERs). Two isoforms of the estrogen receptor, alpha and beta are present in the rat hippocampus and distinct effects on cognitive behavior have been described for each receptor. The present study generated a profile of synaptic proteins altered by administration of estradiol benzoate, the ERalpha selective agonist PPT (1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole) and the ERbeta selective agonist DPN (2,3-bis (4-hydroxyphenyl) propionitrile) alone and in combination in comparison to vehicle in the CA1 region of the dorsal hippocampus. In the stratum radiatum, estradiol, DPN, and PPT increased PSD-95 and AMPA-type glutamate receptor subunit GluR1. Only DPN administration regulated expression of AMPA receptor subunits GluR2 and GluR3, increasing and decreasing levels respectively. DPN also increased GluR2 expression in the other lamina of the CA1. These results support previous reports that estradiol and isoform specific agonists differentially activate ERalpha and ERbeta to regulate protein expression. The distinct effects of DPN and PPT administration on synaptic proteins suggest that the desired therapeutic outcome of estrogen may be accomplished by using specific estrogen receptor agonists. Moreover, the effects of estradiol treatment on PSD-95 expression are consistent with a growing body of evidence that this postsynaptic protein is a key marker of estrogen action related to spine synapse formation.

MeSH Terms
Analysis of Variance Animals Estradiol/analogs & derivatives,pharmacology Estrogen Receptor alpha/agonists,metabolism Estrogen Receptor beta/agonists,metabolism Estrogens/pharmacology Female Hippocampus/drug effects,metabolism Immunohistochemistry Membrane Proteins/metabolism Nerve Tissue Proteins/metabolism Neurons/drug effects,metabolism Ovariectomy Rats Rats, Sprague-Dawley
Chemicals
Estrogen Receptor alpha Estrogen Receptor beta Estrogens Membrane Proteins Nerve Tissue Proteins estradiol 3-benzoate Estradiol
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Waters Elizabeth M
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. [email protected]
Mitterling Katherine
Spencer Joanna L
Mazid Sanoara
McEwen Bruce S
Milner Teresa A
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Article Info
Journal
Brain research
Abbr.
Brain Res
ISSN
1872-6240
DOI
10.1016/j.brainres.2009.06.090
Email
[email protected]
Published
2009-09-22
Epub
2009-00-09
Pages
1-11
Language
English
Region
Netherlands
NLM ID
0045503
PMCID
PMC2778245
Subset
IM
Grants
NINDS NIH HHS · R01 NS007080 · United States
NIDA NIH HHS · R01 DA008259 · United States
NIDDK NIH HHS · T32 DK007313 · United States
NIGMS NIH HHS · T32 GM007739 · United States
NINDS NIH HHS · R01 NS007080-42 · United States
NHLBI NIH HHS · P01 HL018974 · United States
External Links
PubMed source DOI: 10.1016/j.brainres.2009.06.090 PMC Full Text View journal details
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