title: Structure-function-behavior relationship in estrogen-induced synaptic plasticity.
abstract: 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.
authors.affiliation: Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Vierk
authors.affiliation: Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Bayer
authors.affiliation: Department of Molecular Neurogenetics, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20151 Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Freitag
authors.affiliation: Department of Molecular Neurogenetics, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20151 Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Muhia
authors.affiliation: Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kutsche
authors.affiliation: Center for Behavioral Brain Sciences, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Wolbers
authors.affiliation: Department of Molecular Neurogenetics, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20151 Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kneussel
authors.affiliation: Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: tsommer@uke.de.
authors.forename: T
authors.initials: T
authors.lastname: Sommer
authors.affiliation: Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: rune@uke.de.
authors.forename: G M
authors.initials: GM
authors.lastname: Rune
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D000077289:Letrozole; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D004958:Estradiol; D000077289:Letrozole; D001141:Aromatase
keywords: Aromatase; CYP19A1; Letrozole; Long-term potentiation; MRI; Morris water maze; Spatial memory task; Verbal source memory task; Voxel-based-morphometry