Impairment of spatial learning by estradiol treatment in female mice is attenuated by estradiol exposure during development
Impairment of spatial learning by estradiol treatment in female mice is attenuated by estradiol exposure during development
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DOI：
10.1016/j.yhbeh.2006.06.005
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发表时间：
2006-12-01
影响因子：
3.5
通讯作者：
Rissman, Emilie F.
中科院分区：
文献类型：
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作者：
Imwalle, D. Bradley;Bateman, Heather L.;Rissman, Emilie F.
高剂量的雌二醇（E-2）会损害卵巢切除小鼠在莫里斯水迷宫中的空间学习能力，但相同剂量对成年去势雄性小鼠没有影响。在这里，我们检验了这样的假设：这种性别差异是由 E-2 的新生儿行为引起的。在实验 1 中，C57BL/6J 幼犬从出生当天到出生后第 3 天，每天接受苯甲酸雌二醇 (EB) 或油注射。成年犬在训练第一天前 28 小时进行腺切除并接受 EB (sc) 或油注射，在莫里斯水迷宫上每天进行四次训练之前 4 小时接受 EB (sc.) 或油注射。雌性在新生儿时就给予油，并且在训练前进行 EB 表现最差。在新生儿时和训练前接受 EB 治疗的女性对成人 EB 的有害影响不敏感，并且比接受相同激素治疗的男性表现更好。我们使用芳香酶基因敲除 (ArKO) 小鼠进行了第二个实验。成年雄性和雌性 ArKO 以及野生型 (WT) 同窝动物被切除性腺，并在水迷宫训练之前和期间接受油或 EB 注射（如上所述）。激素治疗未能影响表现，然而，与 WT 同窝小鼠相比，雌性而非雄性 ArKO 小鼠表现出学习障碍。因此，在新生儿发育过程中接触雌二醇可以抵消 EB 对成人空间学习的有害影响。 (c) 2006 Elsevier Inc. 保留所有权利。
High doses of estradiol (E-2) can impair spatial learning in the Morris water maze, in ovariectomized mice, but the same dose has no effect on adult castrated males. Here, we test the hypothesis that this sex difference is caused by neonatal actions of E-2. In Experiment 1, C57BL/6J pups were given daily estradiol benzoate (EB) or oil injections from the day of birth until postnatal Day 3. Adults were gonadectomized and received EB (s.c.) or oil 28 h before the first day of training, and 4 h before each of four daily training sessions on the Morris water maze. Females given oil as neonates, and EB prior to training displayed the poorest performance. Females that received EB as neonates and EB prior to training were insensitive to the deleterious effects of adult EB and performed better than males given the same hormone treatments. We conducted a second experiment using aromatase enzyme knockout (ArKO) mice. Adult male and female ArKO and wild-type (WT) littermates were gonadectomized and received either injections of oil or EB prior to and during water maze training (as described above). Hormone treatment failed to affect performance, yet, female but not male ArKO mice showed impaired learning compared to WT littermates. Thus, exposure to estradiol during neonatal development can counteract the deleterious effects of EB on adult spatial learning. (c) 2006 Elsevier Inc. All rights reserved.