High level estradiol impairs and low level estradiol facilitates non-spatial working memory

Wide, Jennifer K.; Hanratty, Katherine; Ting, Julia; Galea, Liisa A.M.

doi:10.1016/j.bbr.2004.04.001

Cited by 85 publications

(51 citation statements)

References 35 publications

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“…On the other hand, earlier studies used either supraphysiological doses of E 2 (ϳ500 pg/ml) (60) or longer E 2 exposure time (21 days) (3). It should be noted that the physiological effects of E 2 are particularly sensitive to specific experimental paradigms (2,11,23,39,53,61), and it is very likely that the discrepancy among these studies arises from differences in steroid dosage and exposure time. Importantly, despite the fact that E 2 effects can be sensitive to the replacement protocol, the present work shows consistent HPA axis effects using two different E 2 replacement methods.…”

Section: Discussionmentioning

confidence: 99%

Estrogen potentiates adrenocortical responses to stress in female rats

Figueiredo

Ulrich‐Lai²,

Choi³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

153

109

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It is well established that estrogens markedly enhance the glucocorticoid response to acute stress in females. However, the precise mechanism responsible for this regulation is poorly understood. Here, we tested whether estrogens enhance the activation of the paraventricular nucleus (PVN) of the hypothalamus by measuring stress-induced c-fos mRNA expression in the PVN of restraint-stressed ovariectomized (OVX) rats treated with physiologically relevant doses of estradiol (E 2), the major female estrogen. As expected, E2 enhanced plasma corticosterone responses to restraint in OVX females. However, E 2 markedly attenuated the stress-induced c-fos gene expression in the PVN and inhibited plasma ACTH responses in these animals. Furthermore, E 2-inhibitory effects were mimicked by progesterone (P) alone or in combination with E 2. Interestingly, the suppressive central effects of both E 2 and P were apparently independent of basal paraventricular corticotropin-releasing hormone (CRH) transcription, since these ovarian steroids did not significantly affect PVN CRH mRNA expression in unstressed rats. These unexpected findings suggested that E 2 promotes glucocorticoid hypersecretion in females by additional peripheral (i.e., adrenal) mechanisms. Indeed, E 2 markedly enhanced plasma corticosterone responses and adrenal corticosterone content in dexamethasone-blocked OVX rats challenged with varying doses of exogenous ACTH. These results suggest that enhanced adrenal sensitive to ACTH is an important physiological mechanism mediating E 2-related glucocorticoid hypersecretion in stressed females.corticosterone; progesterone; c-fos; adrenal; paraventricular nucleus THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS represents an important output in the neuroendocrine response to stress. This axis involves the coordinated activity of parvicellular neurons in the hypothalamic paraventricular nucleus (PVN), adrenocorticotropic hormone (ACTH)-secreting corticotropes in the anterior pituitary, and glucocorticoid-secreting cells in adrenal gland to bring together the neuroendocrine response to stress (1,48,55,56). Activity of the HPA axis is markedly influenced by sex steroids, as illustrated by the pronounced elevations in glucocorticoid levels exhibited in female rodents compared with male counterparts (7, 45). In ovariectomized (OVX) female rats, estradiol (E 2 ) potentiates the corticosterone response to numerous stressors, including restraint (60). Because E 2 -dependent glucocorticoid hypersecretion to a certain extent parallels elevations in ACTH, it is believed (3, 4) that estrogen acts centrally to modulate the neuroendocrine responses to stress.The central sites and mechanisms responsible for E 2 actions on the stress-induced glucocorticoid surge remain elusive. However, there is evidence that altered neuronal activity in the PVN might be involved in mediating E 2 effects on HPA axis responses to stress. In male rats, systemic injections of E 2 enhance the expression of the immediate early gene c-fos in response to novelty...

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Section: Discussionmentioning

confidence: 99%

Estrogen potentiates adrenocortical responses to stress in female rats

Figueiredo

Ulrich‐Lai²,

Choi³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

153

109

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“…Low physiological levels of estradiol facilitate whereas high physiological levels of estradiol impair performance on a nonspatial delayed alternation T-maze (653), a task mediated by the prefrontal cortex and not the hippocampus. There is a delaydependent effect, such that high levels of estradiol impair prefrontal cortex-dependent working memory at longer delays and low levels weakly facilitate prefrontal cortex-dependent working memory at a shorter delay (653). Proestrous levels of estradiol impair performance in the differential reinforcement of low rates of responding task, which assesses prefrontal cortex-mediated response inhibition (641).…”

Section: Estrogens and Prefrontal Cortex-dependent Cognitionmentioning

confidence: 99%

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

Hamson

Roes

Galea

2016

Comprehensive Physiology

173

110

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Sex differences in neurological disease exist in incidence, severity, progression, and symptoms and may ultimately influence treatment. Cognitive disturbances are frequent in neuropsychiatric disease with men showing greater cognitive impairment in schizophrenia, but women showing more severe dementia and cognitive decline with Alzheimer's disease. Although there are no overall differences in intelligence between the sexes, men, and women demonstrate slight but consistent differences in a number of cognitive domains. These include a male advantage, on average, in some types of spatial abilities and a female advantage on some measures of verbal fluency and memory. Sex differences in traits or behaviors generally indicate the involvement of sex hormones, such as androgens and estrogens. We review the literature on whether adult levels of testosterone and estradiol influence spatial ability in both males and females from rodent models to humans. We also include information on estrogens and their ability to modulate verbal memory in men and women. Estrone and progestins are common components of hormone therapies, and we also review the existing literature concerning their effects on cognition. We also review the sex differences in the hippocampus and prefrontal cortex as they relate to cognitive performance in both rodents and humans. There has been greater recognition in the scientific literature that it is important to study both sexes and also to analyze study findings with sex as a variable. Only by examining these sex differences can we progress to finding treatments that will improve the cognitive health of both men and women. © 2016 American Physiological Society. Compr Physiol 6:1295-1337, 2016.

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“…For example, systemic E 2 given acutely or chronically improves spatial working memory in the radial arm maze, the Morris water maze, and alternation or delayed nonmatch to position tasks in the T-maze (O'Neal et al 1996;Daniel et al 1997;Fader et al 1998Fader et al , 1999Luine et al 1998;Bimonte and Denenberg 1999;Gibbs 1999;Daniel and Dohanich 2001;Williams 2001, 2004;Bowman et al 2002;Heikkinen et al 2002;Holmes et al 2002;Garza-Meilandt et al 2006;Bohacek and Daniel 2007;Hammond et al 2009). Nonspatial working memory in the T-maze is also improved by systemic E 2 (Wide et al 2004), as is spatial reference memory in the radial arm and Morris water mazes (Packard and Teather 1997a;Heikkinen et al 2002;Gresack and Frick 2006), recognition memory for the location and identity of objects (Vaucher et al 2002;Luine et al 2003;Walf et al 2006;Frye et al 2007;Fernandez et al 2008;Inagaki et al 2010;Zhao et al 2010;Phan et al 2012;Boulware et al 2013), social recognition memory , inhibitory avoidance (Singh et al 1994;Frye andRhodes 2002, but see Foster et al 2003), and trace eyeblink conditioning (Leuner et al 2004). However, not all studies find that E 2 benefits memory in adult females under all conditions, as improvements often depend on methodological variables such as dose (Packard and Teather 1997a;Holmes et al 2002;Leuner et al 2004;…”

Section: Effects Of Exogenous E 2 On Memory In Femalesmentioning

confidence: 99%

“…Nonspatial working memory in the T-maze is also improved by systemic E 2 (Wide et al 2004), as is spatial reference memory in the radial arm and Morris water mazes (Packard and Teather 1997a;Heikkinen et al 2002;Gresack and Frick 2006), recognition memory for the location and identity of objects (Vaucher et al 2002;Luine et al 2003;Walf et al 2006;Frye et al 2007;Fernandez et al 2008;Inagaki et al 2010;Zhao et al 2010;Phan et al 2012;Boulware et al 2013), social recognition memory , inhibitory avoidance (Singh et al 1994;Frye andRhodes 2002, but see Foster et al 2003), and trace eyeblink conditioning (Leuner et al 2004). However, not all studies find that E 2 benefits memory in adult females under all conditions, as improvements often depend on methodological variables such as dose (Packard and Teather 1997a;Holmes et al 2002;Leuner et al 2004;Wide et al 2004;Gresack and Frick 2006;Foster 2012;Phan et al 2012), age at treatment (Savonenko and Markowska 2003;Gresack et al 2007;Markham and Juraska 2007), duration of treatment (Luine et al 1998;Markowska and Savonenko 2002) (Bohacek and Daniel 2007), the cognitive demands of the task (Bimonte and Denenberg 1999), and duration of ovariectomy prior to treatment (Gibbs 2000;Daniel et al 2006;Vedder et al 2014). Understanding the extent to which these variables influence the response to E 2 has potential translati...…”

Section: Effects Of Exogenous E 2 On Memory In Femalesmentioning

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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High level estradiol impairs and low level estradiol facilitates non-spatial working memory

Cited by 85 publications

References 35 publications

Estrogen potentiates adrenocortical responses to stress in female rats

Estrogen potentiates adrenocortical responses to stress in female rats

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

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

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