Estrogen and Learning

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Science  05 Apr 2002:
Vol. 296, Issue 5565, pp. 15-17
DOI: 10.1126/science.296.5565.15e

Whether and how the hormone estrogen affects cognitive functions has not been clear but has important implications for hormone replacement therapy in women. Current therapy involves the administration of a complex equine estrogen mixture, and its effects appear to include providing some protection against Alzheimer's disease. Estrogen receptors are expressed in the mammalian brain, but estrogen has been reported both to enhance and to impair memory. Mice lacking the estrogen receptor α (ER-α) isoform display some types of behavioral alteration, though not as severely as mice lacking the ER-β isoform.

Rissman et al. report that ER-β knockout female mice learned to escape in a water maze just as well as wild-type females; however, when treated with physiological doses of estrogen, learning was impaired or blocked in the knockout mice. In addition, the knockout mice displayed decreased expression of ER-α in response to estrogen treatment. The authors propose that ER-β may facilitate the positive effects of estrogen on spatial learning and that its absence may increase the negative consequences of estrogen by removing a suppressive effect on ER-α-mediated activities.—LDC

Proc. Natl. Acad. Sci. U.S.A.99, 3996 (2002).

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