ArticlePloS one2012
Increasing hippocampal estrogen receptor alpha levels via viral vectors increases MAP kinase activation and enhances memory in aging rats in the absence of ovarian estrogens.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- High-fat diet attenuates estradiol's efficacy on cognitive function and hippocampal synaptic plasticity in middle-aged ovariectomized mice.Physiological reports · 2026Article
- Estrogen Alleviates Sevoflurane-Induced Neurotoxicity by Inhibiting ERα-Tau Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neuroestrogens, the hippocampus, and female cognitive aging.Hormones and behavior · 2025Review
- Gynecological surgery in adulthood imparts cognitive and brain changes in rats: A focus on hysterectomy at short-, moderate-, and long-term intervals after surgery.Hormones and behavior · 2023Article
- Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging.Frontiers in neuroendocrinology · 2023Review
- Previous estradiol treatment during midlife maintains transcriptional regulation of memory-related proteins by ERα in the hippocampus in a rat model of menopause.Neurobiology of aging · 2021Article
- Estrogen receptor α: a critical role in successful female cognitive aging.Climacteric : the journal of the International Menopause Society · 2021Article
- Surgical Menopause and Estrogen Therapy Modulate the Gut Microbiota, Obesity Markers, and Spatial Memory in Rats.Frontiers in cellular and infection microbiology · 2021Article
- Examination of CA1 Hippocampal DNA Methylation as a Mechanism for Closing of Estrogen's Critical Window.Frontiers in aging neuroscience · 2021Article
- Characterizing the effects of tonic 17β-estradiol administration on spatial learning and memory in the follicle-deplete middle-aged female rat.Hormones and behavior · 2020Article
- Oestradiol as a neuromodulator of learning and memory.Nature reviews. Neuroscience · 2020Review
- A long-term cyclic plus tonic regimen of 17β-estradiol improves the ability to handle a high spatial working memory load in ovariectomized middle-aged female rats.Hormones and behavior · 2020Article
- Nuclear estrogen receptor activation by insulin-like growth factor-1 in Neuro-2A neuroblastoma cells requires endogenous estrogen synthesis and is mediated by mutually repressive MAPK and PI3K cascades.Molecular and cellular endocrinology · 2019Article
- Female Sex Hormones and Cardiac Pressure Overload Independently Contribute to the Cardiogenic Dementia Profile in Yucatan Miniature Swine.Frontiers in cardiovascular medicine · 2019Article
- Lasting impact on memory of midlife exposure to exogenous and endogenous estrogens.Behavioral neuroscience · 2018Article
- Application of a novel social choice paradigm to assess effects of prenatal endocrine-disrupting chemical exposure in rats (Rattus norvegicus).Journal of comparative psychology (Washington, D.C. : 1983) · 2018Article
- Previous estradiol treatment in ovariectomized mice provides lasting enhancement of memory and brain estrogen receptor activity.Hormones and behavior · 2018Article
- Nuclear and membrane estrogen receptor antagonists induce similar mTORC2 activation-reversible changes in synaptic protein expression and actin polymerization in the mouse hippocampus.CNS neuroscience & therapeutics · 2018Article
- Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two.Neurobiology of aging · 2018Article
- Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury.Progress in neurobiology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life estradiol treatment. These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ERα in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ERα (lenti-ERα) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory.
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