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Review
. 2020 May:121:104711.
doi: 10.1016/j.yhbeh.2020.104711. Epub 2020 Feb 13.

Estrogenic regulation of memory: The first 50 years

Victoria Luine  1 , Maya Frankfurt  2
Affiliations
Review

Estrogenic regulation of memory: The first 50 years

Victoria Luine et al. Horm Behav. 2020 May.

Abstract

This review highlights fifty years of progress in research on estradiol's role in regulating behavior(s). It was initially thought that estradiol was only involved in regulating estrus/menstrual cycles and concomitant sexual behavior, but it is now clear that estradiol also influences the higher order neural function of cognition. We provide a brief overview of estradiol's regulation of memory and some mechanisms which underlie its effects. Given systemically or directly into the hippocampus, to ovariectomized female rodents, estradiol or specific agonists, enhance learning and/or memory in a variety of rodent cognitive tasks. Acute (within minutes) or chronic (days) treatments enhance cognitive functions. Under the same treatment conditions, dendritic spine density on pyramidal neurons in the CA1 area of the hippocampus and medial prefrontal cortex increase which suggests that these changes are an important component of estrogen's ability to impact memory processes. Noradrenergic, dopaminergic and serotoninergic activity are also altered in these areas following estrogen treatments. Memory enhancements and increased spine density by estrogens are not limited to females but are also present in castrate males. In the next fifty years, neuroscientists need to determine how currently described neural changes mediate improved memory, how interactions among areas important for memory promote memory and the potential significance of neurally derived estrogens in normal cognitive processing. Answering these questions may provide significant advances for treatment of dementias as well as age and neuro-degenerative disease related memory loss.

Keywords: Dendritic spines; Estrogen; Memory; Monoamines; Plasticity.

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Figures

Figure 1:
Figure 1:
Estradiol enhances learning and/or memory in a variety of rodent tasks A. Water maze – Effects of 5-week treatment with estradiol benzoate (EB, 20,100, 200 ug/kg, S.C.) on (A) escape latency of finding platform and (B) distance traveled reach the platform of OVX mice in water maze. The x-axis denotes each day’s average of four training session. Value differs from the Sham at ## p < 0.001. Value differs from the vehicle-treated OVX group at * P < 0.05 and ** P < 0.01. Reprinted from Zu et al, 2006 by permission. B. Radial arm maze -Effects of estradiol administer prior to and during training on a radial arm maze. OVX rats were implanted with 5 mm Silastics containing 25% estradiol or 100% cholesterol for 30 days prior to and continuing through 24 days of maze training. (A) Mean number of correct arm choices in the first eight visits averaged over 24 days of training (*P < 0.01; ANOVA). (B) Mean number of correct arm choices in the first eight visits presented as 4-day blocks over 24 days of training. Reprinted from Daniel et al, 1997 by permission. C. Object placement memory - Effects of acute E2 and testosterone (T) treatment on place memory in males. Hormones were administered to castrate males immediately following the training trial and were tested two hours later. Time spent exploring objects at old and new location is shown for vehicle- and T-treated, 750 ug/kg (left panel) and vehicle- and E-treated, 20 ug/kg, castrated subjects (right panel). * P < 0.05, by paired t test. Reprinted by permission from Jacome et al, 2016. D. Recognition memory - Effects of chronic estradiol treatment on object and place recognition memory. OVX rats received 2 days of S.C. EB, 50 ug/kg, and object and place memory was tested separately 48 h after the last dose. Entries are ratios (new/old + new) of time spent exploring each object and objects in each location for vehicle and EB-treated subjects. Dotted line at 0.5 indicates spending the same amount of time exploring new and old objects or locations. *** p < 0.001. Data redrawn from Jacome et al (2010). E. Inhibitory Avoidance - Effects of acute E2 on crossover latencies in an inhibitory avoidance test. Crossover latencies are plotted for OVX rats given vehicle (open bars) or estradiol (10 ug) immediately post-training, 0, 1, 2, or 3 h post training and tested 24 h later. * p < 0.05. Redrawn from Rhodes and Frye, 2004.
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