Sex, Hormones and Neurogenesis in the Hippocampus: Hormonal Modulation of Neurogenesis and Potential Functional Implications

Galea, Liisa A.M.; Wainwright, Steven R.; Roes, Meighen; Duarte‐Guterman, Paula; Chow, Carmen; Hamson, Dwayne K.

doi:10.1111/jne.12070

Cited by 190 publications

(153 citation statements)

References 322 publications

(461 reference statements)

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“…Estradiol modulates adult neurogenesis in the dentate gyrus (43,190,194,466,598), which in turn is associated with alterations in hippocampus-dependent cognition (195). In addition, the density of apical dendritic spines in CA1 hippocampal pyramidal cells varies as a function of the estrous cycle in rats and peaks during proestrus (219,667,668).…”

Section: Estrogens and Hippocampal Physiology In Femalesmentioning

confidence: 99%

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

Hamson

Roes

Galea

2016

Comprehensive Physiology

171

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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Section: Estrogens and Hippocampal Physiology In Femalesmentioning

confidence: 99%

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

Hamson

Roes

Galea

2016

Comprehensive Physiology

171

110

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“…Neurogenesis is another major morphological alteration in the hippocampus influenced by E 2 (for reviews, see Galea 2008;Pawluski et al 2009;Galea et al 2013). Among gonadally intact rats, proestrus females transiently exhibit more cell proliferation than males, such that higher numbers of bromodeoxyuridine (BrdU)-labeled cells are observed in females 2 d, but not 14 d, after BrdU injection (Tanapat et al 1999).…”

Section: Neurogenesismentioning

confidence: 99%

“…Nevertheless, it is important that investigators consider the possible effects of sex steroid hormones on neural function and behavior in their experimental designs and data interpretation. However, when thinking about sex differences in brain function or behavior, it is important to note whether differences are due to the activational effects of circulating hormones in adulthood or from organizational effects of hormones in early development, as it has been argued that only the latter can be construed as a true sex difference (McCarthy and Konkle 2005).Numerous recent reviews have discussed the effects of E 2 on learning and memory in females (Korol 2002;Foster 2005;Daniel 2006Daniel , 2013Sherwin and Henry 2008;Barha and Galea 2010;Bimonte-Nelson et al 2010;Gibbs 2010;Kim and Casadesus 2010;Choleris et al 2012;Foster 2012;Frick 2012;Acosta et al 2013;Chisolm and Juraska 2013;Ervin et al 2013;Galea et al 2013;Hogervorst 2013;Luine and Frankfurt 2013;Maki 2013;Bean et al 2014;Luine 2014;Frankfurt and Luine 2015;Tuscher et al 2015). As such, this review will not attempt to provide a comprehensive discussion of all effects of E 2 on learning and memory.…”

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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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“…13,26 In experimental models, estrogens help to increase neurogenesis in the dentate gyrus of the hippocampus and promote a rapid increase of dendritic spine numbers or contacts in the hippocampus, the prefrontal cortex, the medial amygdala and the hypothalamus. 27 In these specific regions, neuronal plasticity helps to maintain cognitive function and protects women from cognitive decline with aging. 14,27 Although both IFN beta and estrogens may improve cognitive function in MS, 6,13 in this study, the lack of a group of patients treated only with estroprogestins leaves uncertainty over the individual contributions of these drugs on preserving/restoring cognition, i.e., whether estroprogestins with high dose estrogens enhance the IFN beta effect or if IFN beta predisposes the immune system to the beneficial effects of estroprogestins.…”

Section: Discussionmentioning

confidence: 99%