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

Abstract

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...

Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice

“…Exogenous estrogens have long been known to regulate many types of learning and memory mediated by the hippocampus and other brain regions (see (Bean et al, 2015; Daniel et al, 2015; Duarte-Guterman et al, 2015; Ervin et al, 2015; Foster, 2012; Frick, 2015; Frick et al, 2015; Korol and Pisani, 2015; Luine, 2014) for recent reviews). The current findings provide novel insight into the functional role of brain-derived estrogens on learning and memory in rodents.…”

Black Cummin Extract (Nigella sativa Linn) on Spatial Memory Performance in Menopausal Model of Rat

“…In addition, at the time of the occurrence of LTP increased protein synthesis and formation of sinap. Estrogen plays a role in increasing LTP in hippocampus (Nyakasa et al 2011;Frick et al 2015) CONCLUSIONS NS extract was not able to improve memory function in ovariectomized rat. This may be caused by short duration of NS exposure and should initiated early within the "critical period" when neurons are healthy and can respond to estrogenic and neuroprotectitive effect of NS.…”

“…In the brain, especially in the hippocampus the RE-β expression is more than RE-α although RE-α and RE-β are both expressed there. Memory function regulation including cholinergic system is through RE-α, while RE-ß modulates RE-α activity (Frick et al 2015). Decreased estrogen causes the role of estrogen in inducing choline acetyltransferase (ChAT) in basal forebrain and hippocampus down (Frick et al 2015).…”

“…Memory function regulation including cholinergic system is through RE-α, while RE-ß modulates RE-α activity (Frick et al 2015). Decreased estrogen causes the role of estrogen in inducing choline acetyltransferase (ChAT) in basal forebrain and hippocampus down (Frick et al 2015). The decrease in ChAT activity in the hippocampus causes the production of acetylcholine (ACh) in the hippocampus to fall, this may be marked by the decrease of several cholinergic markers, including AChE levels.…”

“…The mechanism of action of estrogen in memory function one of them is through the cholinergic system, among others in basal forebrain, estrogen induces ChAT, prevents decreased affinity of up-take choline and ChAT activity in the frontal cortex and hippocampus, influences the transport of neurotropin factor (NGF, BDNF) As a cholinergic system regulator from hippocampus to basal forebrain neurons. In the hippocampus estrogen affects the production of neurotropin factors, increasing the density of the spine dendes in CA1 pyramidal neurons, inducing the formation of new synapses in the spine in CA1, regulating dendritic dendritic spine and the amount of suction on NMDA receptors in CA1, increasing the utilization of glucose by brain cells, Of choline and acetyl coA by increased ChAT enzymes (Frick et al 2015;Daniel, Witty & Rodgers 2015).…”