Molecular mechanisms underlying the memory-enhancing effects of estradiol

Since the publication of the 1998 special issue of Hormones and Behavior on estrogens and cognition, substantial progress has been made towards understanding the molecular mechanisms through which 17 beta-estradiol (E-2) regulates hippocampal plasticity and memory. Recent research has demonstrated that rapid effects of E-2 on hippocampal cell signaling, epigenetic processes, and local protein synthesis are necessary for E-2 to facilitate the consolidation of object recognition and spatial memories in ovariectomized female rodents. These effects appear to be mediated by non-classical actions of the intracellular estrogen receptors ER alpha and ER beta, and possibly by membrane-bound ERs such as the G-protein-coupled estrogen receptor (GPER). New findings also suggest a key role of hippocampally-synthesized E-2 in regulating hippocampal memory formation. The present review discusses these findings in detail and suggests avenues for future study. (C) 2015 Elsevier Inc. All rights reserved.