Structure–function–behavior relationship in estrogen-induced synaptic plasticity

• Published in: Hormones and behavior Vol. 74; pp. 139 - 148
• Main Authors: Vierk, R., Bayer, J., Freitag, S., Muhia, M., Kutsche, K., Wolbers, T., Kneussel, M., Sommer, T., Rune, G.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2015; Elsevier BV
• Subjects: Animals; Aromatase; Aromatase - metabolism; Aromatase Inhibitors - pharmacology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Brain; Cognition - drug effects; Cognition - physiology; CYP19A1; Dendritic Spines - drug effects; Dendritic Spines - physiology; Dendritic Spines - ultrastructure; Estradiol - pharmacology; Estradiol - physiology; Estrogens; Female; Hippocampus - drug effects; Hippocampus - physiology; Humans; Letrozole; Long-term potentiation; Long-Term Potentiation - drug effects; Long-Term Potentiation - genetics; Male; Maze Learning - drug effects; Maze Learning - physiology; Memory - drug effects; Memory - physiology; Mice; Mice, Inbred C57BL; Morphology; Morris water maze; MRI; Neuronal Plasticity - drug effects; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Neurons - drug effects; Neurons - physiology; Nitriles - pharmacology; Rats; Spatial memory task; Synapses - drug effects; Synapses - physiology; Synapses - ultrastructure; Triazoles - pharmacology; Verbal source memory task; Voxel-based-morphometry; Women; Morris water maze; MRI; Aromatase; Long-term potentiation; Spatial memory task; CYP19A1; Letrozole; Verbal source memory task; Voxel-based-morphometry
• ISSN: 0018-506X; 1095-6867
• DOI: 10.1016/j.yhbeh.2015.05.008

This article is part of a Special Issue “Estradiol and Cognition”. In estrogen-induced synaptic plasticity, a correlation of structure, function and behavior in the hippocampus has been widely established. 17ß-estradiol has been shown to increase dendritic spine density on hippocampal neurons and is accompanied by enhanced long-term potentiation and improved performance of animals in hippocampus-dependent memory tests. After inhibition of aromatase, the final enzyme of estradiol synthesis, with letrozole we consistently found a strong and significant impairment of long-term potentiation (LTP) in female mice as early as after six hours of treatment. LTP impairment was followed by loss of hippocampal spine synapses in the hippocampal CA1 area. Interestingly, these effects were not found in male animals. In the Morris water maze test, chronic administration of letrozole did not alter spatial learning and memory in either female or male mice. In humans, analogous effects of estradiol on hippocampal morphology and physiology were observed using neuroimaging techniques. However, similar to our findings in mice, an effect of estradiol on memory performance has not been consistently observed. •LTP and synapse density depend on hippocampus-derived sex steroids.•Local estradiol synthesis is essential for synaptic plasticity in female hippocampus.•Estrogens affect hippocampal morphology in women.