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PMID: 21138734 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Review

GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance.

Brain research ·Vol. 1379 ·2011-03-16 ·Pages 53-60

Hammond R, Gibbs RB

Abstract

Beneficial effects of estrogen therapy on cognitive performance diminish with age and time following the loss of ovarian function. This has led to the 'Window of Opportunity' hypothesis, which states that estrogen therapy must be administered within a limited period of time following menopause in order to be effective. Effects of estrogen therapy on cognitive performance are due, at least in part, to the effects on cholinergic afferents innervating the hippocampus and cortex, and it has been suggested that the loss of estrogen effect with age and time following menopause is due to a substantial reduction in the function of these projections. The mechanisms that underlie the effects are not clear. GPR30 is a novel G-protein coupled estrogen receptor that is expressed in the brain and other tissues. Our recent studies show that GPR30 is expressed in areas of the brain important for spatial learning, memory, and attention. In addition, GPR30 in expressed by the vast majority of cholinergic neurons in the basal forebrain, and appears to be an important regulator of basal forebrain cholinergic function. We hypothesize that GPR30 plays an important role in mediating direct effects of estradiol on basal forebrain cholinergic neurons, with corresponding effects on cognitive performance. Hence, GPR30 may be an important target for developing new therapies that can enhance or restore estrogen effects on cognitive performance in older women. Here we briefly review the cholinergic hypothesis and summarize our findings to date showing effects of a GPR30 agonist and antagonist on basal forebrain cholinergic function and cognitive performance.

MeSH Terms
Animals Cholinergic Fibers/drug effects,physiology Cholinergic Neurons/drug effects,physiology Estrogens/pharmacology,physiology Female Prosencephalon/drug effects,physiology Psychomotor Performance/drug effects,physiology Receptors, Estrogen Receptors, G-Protein-Coupled/agonists,antagonists & inhibitors,physiology
Chemicals
Estrogens GPER1 protein, human Receptors, Estrogen Receptors, G-Protein-Coupled
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hammond R
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA. [email protected]
Gibbs R B
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Article Info
Journal
Brain research
Abbr.
Brain Res
ISSN
1872-6240
DOI
10.1016/j.brainres.2010.11.098
Email
[email protected]
Published
2011-03-16
Epub
2010-00-05
Pages
53-60
Language
English
Region
Netherlands
NLM ID
0045503
PMCID
PMC3046317
Subset
IM
Grants
NIA NIH HHS · F31 AG034035-03 · United States
NIA NIH HHS · R21 AG031794-02 · United States
NIA NIH HHS · F31 AG034035 · United States
NIA NIH HHS · R21 AG031794 · United States
NIA NIH HHS · R36 AG039381 · United States
External Links
PubMed source DOI: 10.1016/j.brainres.2010.11.098 PMC Full Text View journal details
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