title: A Single Neonatal Injection of Ethinyl Estradiol Impairs Passive Avoidance Learning and Reduces Expression of Estrogen Receptor α in the Hippocampus and Cortex of Adult Female Rats.
abstract: Although perinatal exposure of female rats to estrogenic compounds produces irreversible changes in brain function, it is still unclear how the amount and timing of exposure to those substances affect learning function, or if exposure alters estrogen receptor α (ERα) expression in the hippocampus and cortex. In adult female rats, we investigated the effects of neonatal exposure to a model estrogenic compound, ethinyl estradiol (EE), on passive avoidance learning and ERα expression. Female Wistar-Imamichi rats were subcutaneously injected with oil, 0.02 mg/kg EE, 2 mg/kg EE, or 20 mg/kg 17β-estradiol within 24 h after birth. All females were tested for passive avoidance learning at the age of 6 weeks. Neonatal 0.02 mg/kg EE administration significantly disrupted passive avoidance compared with oil treatment in gonadally intact females. In a second experiment, another set of experimental females, treated as described above, was ovariectomized under pentobarbital anesthesia at 10 weeks of age. At 15-17 weeks of age, half of each group received a subcutaneous injection of 5 μg estradiol benzoate a day before the passive avoidance learning test. Passive avoidance learning behavior was impaired by the 0.02 mg/kg EE dose, but notably only in the estradiol benzoate-injected group. At 17-19 weeks of age, hippocampal and cortical samples were collected from rats with or without the 5 μg estradiol benzoate injection, and western blots used to determine ERα expression. A significant decrease in ERα expression was observed in the hippocampus of the estradiol-injected, neonatal EE-treated females. The results demonstrated that exposure to EE immediately after birth decreased learning ability in adult female rats, and that this may be at least partly mediated by the decreased expression of ERα in the hippocampus.
authors.affiliation: School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.
authors.forename: Tatsuomi
authors.initials: T
authors.lastname: Shiga
authors.affiliation: School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.|Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo, Japan.
authors.forename: Takahiro J
authors.initials: TJ
authors.lastname: Nakamura
authors.affiliation: School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Komine
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo, Japan.
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Goto
authors.affiliation: School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mizoguchi
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: School of Life and Environmental Sciences, Teikyo University of Science, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kawaguchi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007279:Injections, Subcutaneous; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; C074283:estradiol 3-benzoate; D004997:Ethinyl Estradiol; D004958:Estradiol