Steroid Hormone Modulation of Hippocampal Dependent Spatial Memory

Abstract

Recent studies show that the adult CNS is capable of considerable re-structuring and re-growth, a property previously thought limited to the developmental period. Hormones play an important role in many of these plastic processes, and the hippocampus, as a target for all the major classes of steroid hormones, undergoes considerable remodeling. Since it is critical for mediating tasks requiring spatial memory, the hippocampus can serve as an important model for understanding not only the mechanisms underlying plasticity of brain circuits but also how these changes impact on a higher order function, spatial memory. In this review, the effects of steroid hormones on hippocampal remodeling are discussed, and the ability of estradiol to enhance spatial memory as well as the ability of both excessive or diminished corticosteroid levels to impair spatial memory are described. The neural mechanisms for these effects, as well as previous and current contributions of McEwen and colleagues to this expanding area of research, are discussed.

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

“…This has been shown for male rats after manipulations that increase estradiol, and the reverse, that learning is worse when estradiol levels are low, for example in aromatase-knockout mice [42]. This has also been studied in female rats after ovariectomy and estradiol replacement, although it is difficult to compare some of these studies because doses of estradiol vary, as well as other potential factors such as age, time after ovariectomy, and housing [5][6][7][8][9][11][12][13]43]. The variability occurs not only in whether behavior is enhanced, but also the type of task.…”

“…The variability occurs not only in whether behavior is enhanced, but also the type of task. Thus, many studies of spatial learning (a classic hippocampal-dependent behavior) show an improvement after estradiol administration, but other types of memory can sometimes also improve, suggesting not only hippocampal effects but also non-hippocampal effects [5][6][7][8][9][11][12][13]43]. Learning appears to be enhanced on the morning of proestrus relative to other cycle stages or relative to ovariectomy [44].…”

Androgens Increase Spine Synapse Density in the CA1 Hippocampal Subfield of Ovariectomized Female Rats

“…Positive associations between endogenous androgen levels and cognitive performance have been reported in men Neave et al, 1999;Yaffe et al, 2002) and women (Barrett-Connor and Goodman-Gruen, 1999). By analogy with the effects of estrogen (Cordoba Montoya and Carrer, 1997; Luine, 1997), enhancement of cognitive function by androgen may result, at least in part, from increased CA1 spine synapse density.…”

Sex Differences in Hippocampal Estradiol-Induced N-Methyl-<i>D</i>-Aspartic Acid Binding and Ultrastructural Localization of Estrogen Receptor-Alpha

“…when estrogen levels are relatively low) [9]. In parallel to these morphological changes, females experiencing estrogenic stimulation, compared to those which are not, exhibit superior performance on certain hippocampal-dependent learning and memory tasks [10,11,12,13,14,15,16,17,18,19,20] and enhanced long-term potentiation, a putative electrophysiological correlate of learning and memory [21,22,23]. Interestingly, there is a sex difference in the effect of estrogen on hippocampal spinogenesis such that estrogen increases spine density and synaptic proteins in adult females, but not in adult males [24, 25].…”