title: Role of estrogen receptor α and β in preserving hippocampal function during aging.
abstract: The expression of the ERα and ERβ estrogen receptors in the hippocampus may be important in the etiology of age-related cognitive decline. To examine the role of ERα and ERβ in regulating transcription and learning, ovariectomized wild-type (WT) and ERα and ERβ knockout (KO) mice were used. Hippocampal gene transcription in young ERαKO mice was similar to WT mice 6 h after a single estradiol treatment. In middle-age ERαKO mice, hormone deprivation was associated with a decrease in the expression of select genes associated with the blood-brain barrier; cyclic estradiol treatment increased transcription of these select genes and improved learning in these mice. In contrast to ERαKO mice, ERβKO mice exhibited a basal hippocampal gene profile similar to WT mice treated with estradiol and, in the absence of estradiol treatment, young and middle-age ERβKO mice exhibited preserved learning on the water maze. The preserved memory performance of middle-age ERβKO mice could be reversed by lentiviral delivery of ERβ to the hippocampus. These results suggest that one function of ERβ is to regulate ERα-mediated transcription in the hippocampus. This model is supported by our observations that knockout of ERβ under conditions of low estradiol allowed ERα-mediated transcription. As estradiol levels increased in the absence of ERα, we observed that other mechanisms, likely including ERβ, regulated transcription and maintained hippocampal-dependent memory. Thus, our results indicate that ERα and ERβ interact with hormone levels to regulate transcription involved in maintaining hippocampal function during aging.
authors: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610-0244, USA.
authors: Xiaoxia
authors: X
authors: Han
authors: Kristina K
authors: KK
authors: Aenlle
authors: Linda A
authors: LA
authors: Bean
authors: Asha
authors: A
authors: Rani
authors: Susan L
authors: SL
authors: Semple-Rowland
authors: Ashok
authors: A
authors: Kumar
authors: Thomas C
authors: TC
authors: Foster
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D047628:Estrogen Receptor alpha / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta
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