Disruption of estrogen receptor beta gene impairs spatial learning in female mice.
Here we provide the first evidence, to our knowledge, that estradiol (E(2)) affects learning and memory via the newly discovered estrogen receptor beta (ERbeta). In this study, ERbeta knockout (ERbetaKO) and wild-type littermates were tested for spatial learning in the Morris water maze after ovariectomy, appropriate control treatment, or one of two physiological doses of E(2). Regardless of treatment, all wild-type females displayed significant learning. However, ERbetaKOs given the low dose of E(2) were delayed in learning acquisition, and ERbetaKOs administered the higher dose of E(2) failed to learn the task. These data show that ERbeta is required for optimal spatial learning and may have implications for hormone replacement therapy in women.
Rissman
Emilie F
EF
Department of Biology and Internal Medicine, University of Virginia, Charlottesville, VA 22903, USA. efr2@virginia.edu
Heck
Amy L
AL
Leonard
Julie E
JE
Shupnik
Margaret A
MA
Gustafsson
Jan-Ake
JA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003463:Cues; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D047629:Estrogen Receptor beta; D005260:Female; D017353:Gene Deletion; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D004958:Estradiol