Role of estrogen receptor alpha and beta expression and signaling on cognitive function during aging
Open accessAbstract
This review presents evidence for the idea that the expression of estrogen receptor alpha and beta (ERα and ERβ) interacts with the level of estradiol (E2) to influence the etiology of age‐related cognitive decline and responsiveness to E2 treatments. There is a nonmonotonic dose response curve for E2 influences on behavior and transcription. Evidence is mounting to indicate that the dose response curve is shifted according to the relative expression of ERα and ERβ. Recent work characterizing age‐related changes in the expression of ERα and ERβ in the hippocampus, as well as studies using mutant mice, and viral mediated delivery of estrogen receptors indicate that an age‐related shift in ERα/ERβ expression, combined with declining gonadal E2 can impact transcription, cell signaling, neuroprotection, and neuronal growth. Finally, the role of ERα/ERβ on rapid E2 signaling and synaptogenesis as it relates to hippocampal aging is discussed. © 2011 Wiley Periodicals, Inc.
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Normal aging is accompanied by reductions in gray matter volume and functional changes in prefrontal, medial temporal, and parietal cortices.
“magnetic resonance imaging (MRI) studies have shown that normal aging is associated with gray matter volume reductions and functional alterations in several regions critical for higher cognitive function: prefrontal, medial temporal and parietal cortices.21–24”
From Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing (2018) · cites this paper as [22]
The paper’s section on ERα and ERβ expression and E2-induced synaptogenesis discusses age-related synaptic and memory changes, not MRI findings. Searches for gray-matter volume, MRI, and the specified cortical regions found no passage in our copy addressing the claimed regional volume reductions and functional alterations. (LLM, conf=0.75)
Experimental — accuracy not yet measuredSuccessful aging is strongly influenced by genetic programming interacting with endogenous and exogenous hormonal changes.
“Successful aging is highly influenced by the interaction of genetic programming with endogenous and exogenous (i.e., hormonal replacement) hormonal changes.(Bean, Ianov, and Foster 2014;Foster 2012)”
From Successful aging: Advancing the science of physical independence in older adults (2015) · cites this paper as Foster 2012
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- Authors
- Foster, T. C.
- Affiliations
- University of Florida (US)
- Corresponding author
- Foster, Thomas C.
- ORCID
- Foster, Thomas C.
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2011-04-27
- Volume
- 22
- Issue
- 4
- Pages
- 656-669
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- PMC
- PMC3704216
- OpenAlex
- W2037611373
- Cited by
- 231
- References
- 205
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 17 · 2022: 22 · 2021: 18 · 2020: 25 · 2019: 17 · 2018: 16 · 2017: 12 · 2016: 19 · 2015: 18 · 2014: 16 · 2013: 12 · 2012: 7
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG037984, R01AG037984, R01AG014979, AG 14979, R37AG036800, R56AG037984, AG036800, P30AG028740)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- estrogen receptor alpha, estrogen receptor beta, estradiol, age-related cognitive decline, estrogen signaling, neuroprotection, synaptogenesis, rapid estrogen signaling
- MeSH terms
- Aging, Animals, Cognition, Estradiol, Female, Humans, Memory, Memory Disorders, Models, Biological, Models, Psychological, Signal Transduction, Mice, Knockout, Estrogen Receptor alpha, Estrogen Receptor beta, Mice, Rats, Neurogenesis
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