| First Author | Han X | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 6 | Pages | 2671-83 |
| PubMed ID | 23392694 | Mgi Jnum | J:194268 |
| Mgi Id | MGI:5471885 | Doi | 10.1523/JNEUROSCI.4937-12.2013 |
| Citation | Han X, et al. (2013) Role of estrogen receptor alpha and beta in preserving hippocampal function during aging. J Neurosci 33(6):2671-83 |
| abstractText | The expression of the ERalpha and ERbeta estrogen receptors in the hippocampus may be important in the etiology of age-related cognitive decline. To examine the role of ERalpha and ERbeta in regulating transcription and learning, ovariectomized wild-type (WT) and ERalpha and ERbeta knockout (KO) mice were used. Hippocampal gene transcription in young ERalphaKO mice was similar to WT mice 6 h after a single estradiol treatment. In middle-age ERalphaKO 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 ERalphaKO mice, ERbetaKO 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 ERbetaKO mice exhibited preserved learning on the water maze. The preserved memory performance of middle-age ERbetaKO mice could be reversed by lentiviral delivery of ERbeta to the hippocampus. These results suggest that one function of ERbeta is to regulate ERalpha-mediated transcription in the hippocampus. This model is supported by our observations that knockout of ERbeta under conditions of low estradiol allowed ERalpha-mediated transcription. As estradiol levels increased in the absence of ERalpha, we observed that other mechanisms, likely including ERbeta, regulated transcription and maintained hippocampal-dependent memory. Thus, our results indicate that ERalpha and ERbeta interact with hormone levels to regulate transcription involved in maintaining hippocampal function during aging. |
