Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats
Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats
复制标题
DOI：
10.1038/npp.2009.161
复制
发表时间：
2010-01-01
影响因子：
7.6
通讯作者：
Galea, Liisa A. M.
中科院分区：
文献类型：
--
作者：
Barha, Cindy K.;Dalton, Gemma L.;Galea, Liisa A. M.
雌激素对成年啮齿动物的海马具有重要的结构和功能影响。特别是，17 -雌二醇对海马依赖性学习和记忆的改善、损害或无影响取决于给药的剂量和时间。其他形式的雌激素，如雌酮和17 -雌二醇，对海马体依赖性学习的影响还没有得到彻底的研究。因此，本研究的目的是研究三种不同剂量的17 -雌二醇、雌酮和17 -雌二醇在两种不同任务中的作用：海马体依赖的情境恐惧条件反射和海马体独立的线索恐惧条件反射。切除卵巢的成年雌性大鼠在调节前30分钟注射三种剂量中的一种雌激素，以评估这些雌激素对获取的快速影响。24小时后检查对情境的记忆，1小时后评估对提示（音调）的记忆。研究人员检测了大鼠海马背侧突触素的水平，以确定激素对情境恐惧条件反射的潜在突触相关性。低-雌二醇和α -雌二醇水平增强，而高-雌二醇和α -雌二醇水平削弱情境恐惧条件反射。只有中等剂量的雌酮严重损害了情境恐惧条件反射。雌激素并没有改变海马独立提示任务的表现。雌酮（中剂量和高剂量）和17 β -雌二醇（中剂量）在海马CA3区增加了Synaptophysin的表达，但与认知无关。本研究结果表明，雌二醇对海马依赖性学习记忆有正向或负向影响，而雌酮对海马依赖性学习记忆的影响呈剂量依赖性。这些结果具有重要的治疗意义，因为雌酮，广泛使用的激素替代疗法的主要成分，被证明对学习和记忆有负面影响或没有影响。使用17 -雌二醇和低剂量的雌激素作为激素替代疗法的潜在替代品是可能的。神经精神药理学（2010）35,547-559；doi: 10.1038 / npp.2009.161;2009年10月21日在线发布
Estrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. In particular, 17 beta-estradiol can improve, impair, or have no effect on hippocampus-dependent learning and memory depending on dose and time of administration. The effects of other forms of estrogen, such as estrone and 17 alpha-estradiol, on hippocampus-dependent learning have not been as thoroughly investigated. Therefore, the purpose of this study was to investigate the effects of 17 beta-estradiol, estrone, and 17 alpha-estradiol at three different doses on two different tasks: hippocampus-dependent contextual fear conditioning and hippocampus-independent cued fear conditioning. Adult ovariectomized female rats were injected with one of the estrogens at one of the three doses 30 mins before conditioning to assess the rapid effects of these estrogens on acquisition. Twenty-four hours later memory for the context was examined and 1 h later memory for the cue (tone) was assessed. Levels of synaptophysin were examined in the dorsal hippocampus of rats to identify a potential synaptic correlate of hormonal effects on contextual fear conditioning. Low 17 beta-estradiol and 17 alpha-estradiol enhanced, whereas high 17 beta-estradiol and 17 alpha-estradiol impaired, contextual fear conditioning. Only the middle dose of estrone severely impaired contextual fear conditioning. Estrogens did not alter performance in the hippocampus-independent cued task. Synaptophysin expression was increased by estrone (at a middle and high dose) and 17 beta-estradiol (at a middle dose) in the CA3 region of the hippocampus and was not correlated with cognition. The results of this study indicate that estradiol can positively or negatively influence hippocampus-dependent learning and memory, whereas estrone impairs hippocampus-dependent learning and memory in a dose-dependent manner. These results have important therapeutic implications, as estrone, a main component of a widely used hormone replacement therapy, was shown to have either a negative effect or no effect on learning and memory. It may be possible to use 17 alpha-estradiol and lower doses of estrogens as potential alternatives in hormone replacement therapies. Neuropsychopharmacology (2010) 35, 547-559; doi: 10.1038/npp.2009.161; published online 21 October 2009