Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats1First published on the World Wide Web on 4 November 1997.1

Montoya, Daniel; Carrer, Hugo F.

doi:10.1016/s0006-8993(97)01206-7

Cited by 190 publications

(70 citation statements)

References 48 publications

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“…Finally, it is possible that ER in certain dendritic spines might "tag" those spines for specific signal effects of estrogens in relation to LTP and forms of synaptic plasticity. In support of this assertion, facilitation of LTP by estrogen treatment or during the ovarian cycle has been reported (Warren et al, 1995;Cordoba-Montoya et al, 1997).…”

Section: Extranuclear Er␣-i Is Prominent In Dendritic Spinesmentioning

confidence: 74%

Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites

et al. 2000

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Estrogen may mediate some of its effects on hippocampal function through the alpha isoform of the estrogen receptor (ERalpha). By light microscopy, ERalpha-immunoreactivity (-I) is found in the nuclei of scattered inhibitory gamma-aminobutyric acid (GABA)ergic interneurons. However, several lines of evidence indicate that estrogen also may exert some of its effects through rapid nongenomic mechanisms, possibly by binding to plasma membranes. Thus, to determine whether ERalpha is found in extranuclear sites in the hippocampal formation (HF), four different antibodies to ERalpha were localized by immunoelectron microscopy in proestrous rats. Ultrastructural analysis revealed that in addition to interneuronal nuclei, ERalpha-I was affiliated with the cytoplasmic plasmalemma of select interneurons and with endosomes of a subset of principal (pyramidal and granule) cells. Moreover, ERalpha labeling was found in profiles dispersed throughout the HF, but slightly more numerous in CA1 stratum radiatum. Approximately 50% of the ERalpha-labeled profiles were unmyelinated axons and axon terminals that contained numerous small, synaptic vesicles. ERalpha-labeled terminals formed both asymmetric and symmetric synapses on dendritic shafts and spines, suggesting that ERalphas arise from sources in addition to inhibitory interneurons. About 25% of the ERalpha-I was found in dendritic spines, many originating from principal cells. Within spines, ERalpha-I often was associated with spine apparati and/or polyribosomes, suggesting that estrogen might act locally through the ERalpha to influence calcium availability, protein translation, or synaptic growth. The remaining 25% of ERalpha-labeled profiles were astrocytes, often located near the spines of principal cells. Collectively, these results suggest that ERalpha may serve as both a genomic and nongenomic transducer of estrogen action in the HF.

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Section: Extranuclear Er␣-i Is Prominent In Dendritic Spinesmentioning

confidence: 74%

Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites

et al. 2000

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“…Within the rat estrous cycle, the greatest degree of LTP in CA1 is observed on the afternoon of proestrus, at which point estrogen and progesterone levels peak (Warren et al 1995). Similarly, exogenous E 2 increases baseline EPSP amplitude, reduces the threshold for LTP, and increases LTP amplitude in the hippocampus of male and female rodents (Teyler et al 1980;Cordoba-Montoya and Carrer 1997;Foy et al 1999Foy et al , 2008Bi et al 2000;Fugger et al 2001;Sharrow et al 2002;McMahon 2005, 2006;Kramár et al 2009;Smejkalova and Woolley 2010;Tanaka and Sokabe 2013;Kumar et al 2015). Bath-applied E 2 and PPT facilitated NMDA-mediated transmission and LTP in the dentate gyrus of slices from juvenile males, whereas DPN suppressed both forms of plasticity Sokabe 2012, 2013).…”

Section: Synaptic Plasticitymentioning

confidence: 99%

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

et al. 2015

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Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17b-estradiol (E 2 ), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E 2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E 2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E 2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs.Hormones have long been known to play key roles in regulating learning and memory. Many hormones, including epinephrine, glucocorticoids, and insulin influence learning and memory via inverted U-shaped dose-response relationships in which memory is enhanced by moderate, but not low or high, hormone levels (Roozendaal 2000;Korol and Gold 2007;McNay and Recknagel 2011). Research from the past two decades has demonstrated that sex steroid hormones, particularly the potent estrogen 17b-estradiol (E 2 ), also regulate learning and memory in male and female rodents via an inverted U-shaped dose-response function that is influenced by estrogen receptor expression (Packard and Teather 1997a;Packard 1998;Foster 2012). Yet E 2 has not gained widespread acceptance as a hormonal modulator of memory in both females and males, perhaps because the majority of this research has been conducted in female rodents. Moreover, the common view of E 2 as a "female" hormone may contribute to the misperception that E 2 is not relevant for cognitive function in males. However, considerable evidence supports a vital role for E 2 in mediating neural function and behavior in male rodents. Therefore, it is important for investigators working with males to understand the ways in which E 2 and other sex steroid hormones (e.g., androgens, progestins, and other estrogens) may influence their brain regions and behaviors of interest.Another reason for investigators to be cognizant of sex steroid hormone-induced regulation of learning and memory is that males and females may respond differently to various treatments and environmental factors. A classic example is that of acute stress, which enhances classical conditioning and increases apical CA1 dendritic spine density in male rats, but impairs classical conditioning and decreases CA1 spine density in female rats (Wood and Shors 1998;Shors et al. 2001). Therefore, investigators hoping to comply with National Institutes of Health policies that encourage the inclusion of females in biomedical research must be aware that adding females to a study is not as simple as adding another group. In some ways, females are fundamentally different from males, the most obvious of which is the presence of reproductive...

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“…The effects of estradiol on spine density and LTP were frequently shown by either using ovariectomized animals, which had been treated systemically with estradiol (Gould et al, 1990;Warren et al, 1995;Có rdoba Montoya and Carrer, 1997;Smith and McMahon, 2005;Kramár et al, 2009), by applying estradiol to acute slices of mostly male rats (Foy et al, 1999;Ito et al, 1999;Mukai et al, 2007;Kramár et al, 2009), or by using mixed hippocampal slice cultures from neonatal males and females (Murphy and Segal, 1996;Kretz et al, 2004;Mendez et al, 2011). Thus, the vast majority of studies do not consider the potential differences between males and females.…”

Section: Introductionmentioning

confidence: 99%

Aromatase Inhibition Abolishes LTP Generation in Female But Not in Male Mice

Vierk

Glassmeier²,

Zhou³

et al. 2012

Journal of Neuroscience

149

137

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Inhibitors of aromatase, the final enzyme of estradiol synthesis, are suspected of inducing memory deficits in women. In previous experiments, we found hippocampal spine synapse loss in female mice that had been treated with letrozole, a potent aromatase inhibitor. In this study, we therefore focused on the effects of letrozole on long-term potentiation (LTP), which is an electrophysiological parameter of memory and is known to induce spines, and on phosphorylation of cofilin, which stabilizes the spine cytoskeleton and is required for LTP in mice. In acute slices of letrozole-treated female mice with reduced estradiol serum concentrations, impairment of LTP started as early as after 6 h of treatment and progressed further, together with dephosphorylation of cofilin in the same slices. Theta-burst stimulation failed to induce LTP after 1 week of treatment. Impairment of LTP was followed by spine and spine synapse loss. The effects were confirmed in vitro by using hippocampal slice cultures of female mice. The sequence of effects in response to letrozole were similar in ovariectomized female and male mice, with, however, differences as to the degree of downregulation. Our data strongly suggest that impairment of LTP, followed by loss of mushroom spines and spine synapses in females, may have implications for memory deficits in women treated with letrozole.

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Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats1First published on the World Wide Web on 4 November 1997.1

Cited by 190 publications

References 48 publications

Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites

Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

Aromatase Inhibition Abolishes LTP Generation in Female But Not in Male Mice

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