Modulation of synaptic plasticity in the hippocampus by hippocampus-derived estrogen and androgen

Ooishi, Yuuki; Kawato, Suguru; Hojo, Yasushi; Hatanaka, Yusuke; Higo, Shimpei; Murakami, Gen; Komatsuzaki, Yoshimasa; Ogiue-Ikeda, Mari; Kimoto, Tsunenobu; Mukai, Hideo

doi:10.1016/j.jsbmb.2011.10.004

Cited by 110 publications

(94 citation statements)

References 111 publications

(232 reference statements)

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“…The effects of androgens on spines are supported by data from male hippocampal slices showing that bath application of testosterone or the nonaromatizable DHT also increased CA1 spine density (Ooishi et al 2012;Hatanaka et al 2014). In contrast to the in vivo data, however, studies using hippocampal slices from adult male rats report that the density of dendritic spines in CA1 was increased within 2 h of bath application of E 2 (Murakami et al 2006Mukai et al 2007;Ogiue-Ikeda et al 2008;Ooishi et al 2012). This increase was blocked by an inhibitor of ERK phosphorylation (Mukai et al 2007;Murakami et al 2014), linking ERK signaling to E 2 -induced CA1 spinogenesis in males.…”

Section: Spine Densitymentioning

confidence: 84%

“…Similarly, an E 2 -induced increase in cortical dendritic spine density observed 30 min after bath application in embryonic rat cultures was blocked by pharmacological inhibition of Rap/AF-6/ ERK signaling (Srivastava et al 2008). As with E 2 , the spine increase induced by testosterone and DHT in males was blocked by inhibitors of ERK, PKA, PKC, LIM kinase (LIMK), and calcineurin (Ooishi et al 2012;Hatanaka et al 2014). As will be discussed below (see "Molecular mechanisms underlying E 2 's effects on memory consolidation"), many of these same signaling cascades are involved in estrogenic regulation of hippocampal memory consolidation in ovariectomized mice, potentially linking E 2 -induced alterations in CA1 spine density and LTP with memory formation.…”

Section: Spine Densitymentioning

confidence: 86%

“…Rather, the gonadectomy-induced decrease was reversed by 2 d of systemic testosterone or the nonaromatizable androgen dihydrotestosterone (DHT) (Leranth et al 2003). The effects of androgens on spines are supported by data from male hippocampal slices showing that bath application of testosterone or the nonaromatizable DHT also increased CA1 spine density (Ooishi et al 2012;Hatanaka et al 2014). In contrast to the in vivo data, however, studies using hippocampal slices from adult male rats report that the density of dendritic spines in CA1 was increased within 2 h of bath application of E 2 (Murakami et al 2006Mukai et al 2007;Ogiue-Ikeda et al 2008;Ooishi et al 2012).…”

Section: Spine Densitymentioning

confidence: 98%

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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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Section: Spine Densitymentioning

confidence: 84%

Section: Spine Densitymentioning

confidence: 86%

Section: Spine Densitymentioning

confidence: 98%

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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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“…Gonadal steroids can regulate the morphology and activity of the hippocampus by activating specific neuronal receptors [33,34] that are present in the rat at the embryonic stage [35]. Sex steroids can be synthesized within the hippocampus [36], but the morphology of hippocampal pyramidal cells and spatial learning can also be affected by manipulation of circulating levels of testosterone and estradiol [37]. …”

Section: Introductionmentioning

confidence: 99%

“…The expression of GluR1 in the hippocampus declines in association with deterioration in spatial learning in aged rats [50]. Both GluR1-receptor-mediated activity [51] and that of neuronal nitric oxide synthase (nNOS), which catalyzes the formation of NO, is also sensitive to the action of estradiol [52] formed within hippocampal neurons [36]. …”

Section: Introductionmentioning

confidence: 99%

Sex-Specific Effects of Prenatal Stress on Memory and Markers of Neuronal Activity in Juvenile Rats

Barbie-Shoshani

Shoham²,

Bejar³

et al. 2016

Dev Neurosci

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Stress during pregnancy can increase the incidence of emotional problems, learning and language difficulties in human infants and pre-adolescents. Most preclinical studies in rats that attempted to find experimental support for these observations were performed in adult male offspring, but the results are inconsistent. The aim of the current study was to examine the effect of prenatal stress on novel object recognition (NOR) and spatial learning and memory in the Morris water maze (MWM) of juvenile rats of both sexes. By the use of fluorescence immunohistochemistry and protein measurements by Western blot, we measured the expression of markers of neurogenesis (doublecortin, DCX) and neuronal activity that are important for synaptic plasticity and learning (c-fos, GluR1, nNOS). Since neuronal activity in the developing and adult brain can be regulated by astrocytes, we also measured the number of astrocytes and the expression of two astroglial proteins (GFAP and S100B) in the stress-responsive hippocampal dentate gyrus (DG). Experiments were performed on littermates of rats in which its effects on behavior were measured. We found for the first time that juvenile females performed better than males in the NOR and MWM tests. They also had higher densities of DCX and c-fos in the DG, together with the expression of nNOS and GluR1 in the subgranular zone (SGZ) of the DG. There were no sex differences in the expression of GFAP and S100B in astrocytes. Prenatal stress did not affect NOR in females, but improved it in males, together with an increase in DCX+ and c-fos, the number of GFAP-expressing astrocytes and the intensity of GFAP and S100B immunofluorescence in the DG. Staining intensity of GluR1 and nNOS in the hilus and SGZ of the DG, and protein expression in the whole DG, was unchanged in prenatally stressed males. Thus, prenatal stress changed the behavior and expression of key proteins in the DG to resemble that in females. A reduction in plasma testosterone, which although not attaining statistical significance was associated with that in anogenital distance, may contribute to the effect of prenatal stress in males. In females, prenatal stress had no effect on c-fos, DCX or the number of astrocytes but reduced the staining intensity of GluR1 and nNOS. Protein expression of nNOS was also significantly lower than that in prenatally stressed males. The differential effects of prenatal stress on hippocampal neuronal and glial markers may help to explain the sex-dependent effect on spatial learning in prepubertal rats.

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The effect of neuroactive steroids in sex differences in the developmental neurotoxicity of the anaesthetic

Zhu

Zeng

et al. 2022

Clinical and Translational Dis

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The rapid growth of the number of surgical cases in the world has brought opportunities and challenges to the development of anaesthesia. Modern anaesthesia technology provides safe and effective anaesthesia for hundreds of millions of surgical procedures each year, but there is a lot of concern about the complications (mainly cognitive dysfunction) that occur after anaesthesia exposure. Preclinical studies have demonstrated cognitive dysfunction and behavioural abnormalities that persist into adulthood after exposure to anaesthesia in rodents, revealing the potential neurotoxicity of anaesthetic drugs. In a further study, Sprague-Dawley rats treated with sevoflurane in the first week of life were then subjected to behavioural tests, and female rats were significantly more negatively affected in spatial learning than male rats, suggesting that there may be gender differences in neurotoxicity of the anaesthetic, but the specific mechanisms are unclear. According to the available data, the main hypothesis that can explain the sex difference in the effect of anaesthesia on the central nervous system development remains the difference in hormone levels between males and females. Therefore, this review briefly describes the role of neuroactive steroids in the mechanism of sex differences in neurotoxicity during the development of general anaesthetics.

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Modulation of synaptic plasticity in the hippocampus by hippocampus-derived estrogen and androgen

Cited by 110 publications

References 111 publications

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

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

Sex-Specific Effects of Prenatal Stress on Memory and Markers of Neuronal Activity in Juvenile Rats

The effect of neuroactive steroids in sex differences in the developmental neurotoxicity of the anaesthetic

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