Rissman Emilie F, Heck Amy L, Leonard Julie E, Shupnik Margaret A, Gustafsson Jan-Ake
Department of Biology and Internal Medicine, University of Virginia, Charlottesville, VA 22903, USA.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3996-4001. doi: 10.1073/pnas.012032699. Epub 2002 Mar 12.
Here we provide the first evidence, to our knowledge, that estradiol (E(2)) affects learning and memory via the newly discovered estrogen receptor beta (ERbeta). In this study, ERbeta knockout (ERbetaKO) and wild-type littermates were tested for spatial learning in the Morris water maze after ovariectomy, appropriate control treatment, or one of two physiological doses of E(2). Regardless of treatment, all wild-type females displayed significant learning. However, ERbetaKOs given the low dose of E(2) were delayed in learning acquisition, and ERbetaKOs administered the higher dose of E(2) failed to learn the task. These data show that ERbeta is required for optimal spatial learning and may have implications for hormone replacement therapy in women.
据我们所知，我们在此首次提供证据表明，雌二醇（E₂）通过新发现的雌激素受体β（ERβ）影响学习和记忆。在本研究中，对卵巢切除术后、接受适当对照处理或接受两种生理剂量E₂之一的ERβ基因敲除（ERβKO）小鼠及其野生型同窝小鼠进行了Morris水迷宫空间学习测试。无论处理方式如何，所有野生型雌性小鼠均表现出显著的学习能力。然而，给予低剂量E₂的ERβKO小鼠在学习获取方面出现延迟，而给予高剂量E₂的ERβKO小鼠未能学会该任务。这些数据表明，ERβ是最佳空间学习所必需的，可能对女性激素替代疗法具有重要意义。
