Corrieri Luca, Della Seta Daniele, Canoine Virginie, Fusani Leonida
Dipartimento di Fisiologia, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
Horm Behav. 2007 May;51(5):620-5. doi: 10.1016/j.yhbeh.2007.03.002. Epub 2007 Mar 7.
Steroid hormones have profound effects on the development and function of the nervous system. Environmental estrogens or xenoestrogens are manmade or are natural compounds, which mimics the action of estrogen hormones. The experimental evidence for impairment of cognitive functions in humans and mammals following exposure to xenoestrogens has been fiercely debated. The strongest arguments against such studies have been that the route, time course, and intensity of exposure did not simulate environmental exposure, and that the chemicals tested have additional, non-estrogenic toxic effects, hindering a generalization of actual "xenoestrogenic" effects. Here we show that an environmental-like exposure to the pure estrogen, 17alpha-ethynylestradiol (EE2) during development enhances spatial learning abilities in adult male Sprague-Dawley rats. To simulate an environmental exposure, we used a very low dose (4 ng/kg/day) of EE2 equivalent to concentrations measured in European and US streams which was given orally with a non-invasive method, and we extended the treatment for the entire course of development, from conception to puberty. The animals were tested in a Morris water maze protocol at 6 months of age. Male rats treated with EE2 during development showed a faster learning during the training phase, and remembered better the position of the hidden platform in the short term. Our study demonstrates that actual levels of exposure to xenoestrogens can permanently alter cognitive abilities of a mammalian species.
类固醇激素对神经系统的发育和功能具有深远影响。环境雌激素或外源性雌激素是人造或天然化合物,它们模拟雌激素的作用。关于人类和哺乳动物在接触外源性雌激素后认知功能受损的实验证据一直存在激烈争论。对此类研究最有力的反对观点是,接触的途径、时间进程和强度并未模拟环境暴露,而且所测试的化学物质具有额外的非雌激素毒性作用,这阻碍了对实际“外源性雌激素”效应的概括。在此我们表明,在发育过程中模拟环境暴露给予纯雌激素17α-乙炔基雌二醇(EE2)可增强成年雄性Sprague-Dawley大鼠的空间学习能力。为模拟环境暴露,我们使用了极低剂量(4纳克/千克/天)的EE2,其相当于在欧洲和美国溪流中测得的浓度,采用非侵入性方法经口给予,并且将治疗扩展至从受孕到青春期的整个发育过程。在6个月大时,对这些动物进行莫里斯水迷宫实验。在发育过程中接受EE2治疗的雄性大鼠在训练阶段学习速度更快,并且在短期内对隐藏平台位置的记忆更好。我们的研究表明,实际接触外源性雌激素的水平可永久性改变哺乳动物的认知能力。