Researchers have known for two decades that the sex steroid hormone 17beta-estradiol alters the morphology of neurons in the hippocampus and prefrontal cortex, parts of the brain necessary for memory formation that deteriorate in aging and Alzheimer’s disease. In particular, estradiol increases the density of spines on the dendrites of excitatory neurons in the hippocampus and cortex. Dendritic spines are associated with greater synaptic plasticity, so an increase in dendritic spines is thought to underlie the enhanced memory observed after estradiol treatment in rodents. However, it has been unknown how estradiol regulates dendritic spines. A recent study published in The Journal of Neuroscience by Dr. Karyn Frick and graduate student Jennifer Tuscher, along with collaborators in New York, sheds light on this mystery. The Frick lab previously showed in mice that the cell-signaling molecules ERK and mTOR played crucial roles in the ability of estradiol to enhance the kinds of spatial memory and object recognition memories mediated by the hippocampus. It turns out that activation of ERK or mTOR signaling in the hippocampus is also necessary for estradiol to increase dendritic spine density not only in the hippocampus, but also the prefrontal cortex. Thus, this study is the first to show that cell signaling regulates estradiol-induced spine formation in the hippocampus, and that this spine formation drives spinogenesis in the prefrontal cortex.

These findings are significant because they provide novel insights into the molecular mechanisms through which estradiol mediates the function of the hippocampus and prefrontal cortex. Women are at greater risk of developing age-related memory decline and dementia than men, likely due to estradiol loss at menopause. Because age-related impairments in hippocampal and cortical function are associated with memory decline, it is important to understand how estradiol regulates the function of these brain regions in females. This knowledge could facilitate the development of new therapies to prevent or reduce memory dysfunction in older women.