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Estradiol enhances some aspects of learning and memory in both humans and animal models. These enhancements are present throughout the adult lifespan (Luine, 2008) and extend into old age (Frick, 2008). While many neurochemicals and neurotrophins have been shown to be regulated by estrogen, the mechanism(s) responsible for estrogen’s positive effects on cognition remain elusive. It has, however, been demonstrated that gonadal hormones, both estrogens and progestins, influence neural morphology in areas important for cognitive function such as the hippocampus and medial prefrontal cortex (PFC). Spines, which are located on the dendrites of pyramidal neurons in both of these areas, have been shown to contribute to cognitive function (Morgado-Bernal, 2011). Therefore, we will review estradiol’s effects on dendritic spine density in the hippocampus and PFC in relation to cognitive function. Moreover, we also consider whether changes in spine density are important for estrogen’s role in the maintenance of memory. The studies are primarily from our own laboratories, but, when available, data from other labs are compared. In our studies, spine density has been investigated by Golgi impregnation, and memory has been evaluated using the spatial memory tasks of radial arm maze and object placement, and non-spatial memory has been assessed by object recognition. In most of the studies to be discussed, both morphology and cognitive function were assessed in the subjects. This current research provides substantial data suggesting a relationship between hormones, spines and cognitive function, but we point out the need for further research to establish causal relationships between these variables and to identify how spines promote memory consolidation and are integrated into memory networks.

An Integrative Review of Estradiol Effects on Dendritic Spines and Memory over the Lifespan