Estrogen-induced plasticity from cells to circuits: predictions for cognitive function

Controversy regarding estrogen action in the brain remains at the forefront of basic, translational and clinical science for women's health. Here, I provide an integrative analysis of estrogen-inducible plasticity and posit it as a strategy for predicting cognitive domains affected by estrogen in addition to sources of variability. Estrogen enhancement of plasticity is evidenced by increases in neurogenesis, neural network connectivity and synaptic transmission. In parallel, estrogen increases glucose transport, aerobic glycolysis and mitochondrial function to provide the ATP necessary to sustain increased energetic demand. The pattern of plasticity predicts that estrogen would preferentially affect cognitive tasks of greater complexity, temporal demand and associative challenge. Thus, estrogen deprivation should be associated with decrements in these functions. Estrogen regulation of plasticity and bioenergetics provides a framework for predicting estrogen-dependent cognitive functions while also identifying sources of variability and potential biomarkers for identifying women appropriate for hormone therapy.