title: Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.
abstract: Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population.
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Alice Shaam
authors.initials: AS
authors.lastname: Al Abed
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Azza
authors.initials: A
authors.lastname: Sellami
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brayda-Bruno
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lamothe
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Noguès
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Potier
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bennetau-Pelissero
authors.affiliation: Neurocentre Magendie, INSERM U1215, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France. Electronic address: aline.marighetto@inserm.fr.
authors.forename: Aline
authors.initials: A
authors.lastname: Marighetto
mesh_terms: D000367:Age Factors; D000375:Aging / Q000187:drug effects; D000818:Animals; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004967:Estrogens; D004958:Estradiol
keywords: Aging; Estrogens; Everyday-like memory; Functional connectivity; Mnemonic update; c-Fos NeuroImaging