Interactions between estradiol, BDNF and dendritic spines in promoting memory.

Several lines of evidence have converged to indicate that memory formation involves plasticity of dendritic spines in the medial prefrontal cortex (PFC) and the hippocampus. Memory varies with estrogen levels throughout the lifespan of the female. Generally, increased levels of estrogen are related to greater dendritic spine density on pyramidal cells in the PFC and the hippocampus and to improved memory function. Brain-derived neurotrophic factor (BDNF) is a growth factor which increases dendritic spines and enhances memory function. Estrogens increase BDNF levels in the PFC and the hippocampus. In the present review we provide evidence that estradiol and BDNF may work in concert to enhance cognition. In adult females, fluctuations in recognition memory following ovariectomy and estradiol replacement, during the estrous cycle, in pregnancy and with aging are accompanied by similar changes in circulating estradiol, BDNF levels and spine density alterations in the PFC and the hippocampus. In addition, both estradiol and BDNF induce spine plasticity via rapid membrane effects and slower transcriptional regulation via the CREB pathway. Moreover, estradiol increases BDNF levels through action on nuclear receptors. While the exact mechanism(s) for the influence of estrogens and BDNF on memory remain unclear, this combination may provide the basis for new and more effective strategies for treating age-related and neurodegenerative memory loss.