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- Title
Role of Estrogen Receptor α and ß in Preserving Hippocampal Function during Aging.
- Authors
Xiaoxia Han; Aenlle, Kristina K.; Bean, Linda A.; Rani, Asha; Semple-Rowland, Susan L.; Kumar, Ashok; Foster, Thomas C.
- Abstract
The expression of the ERα and ERß estrogen receptors in the hippocampus may be important in the etiology of age-related cognitive decline. To examine the role of ERα and ERß in regulating transcription and learning, ovariectomized wild-type (WT) and ERα and ERß 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, ERßKO 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 ERßKO mice exhibited preserved learning on the water maze. The preserved memory performance of middle-age ERßKO mice could be reversed by lentiviral delivery of ERß to the hippocampus. These results suggest that one function of ERß is to regulate ERα-mediated transcription in the hippocampus. This model is supported by our observations that knockout of ERß 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 ERß, regulated transcription and maintained hippocampal-dependent memory. Thus, our results indicate that ERα and ERß intERαct with hormone levels to regulate transcription involved in maintaining hippocampal function during aging.
- Subjects
ESTROGEN receptors; HIPPOCAMPUS (Brain); BLOOD-brain barrier; AGING; ETIOLOGY of diseases; COGNITIVE ability; GENETIC transcription; KNOCKOUT mice
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 6, p2671
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4937-12.2013