Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030-3401, USA.
Mol Pharmacol. 2012 Dec;82(6):1241-9. doi: 10.1124/mol.112.080838. Epub 2012 Sep 18.
Estradiol treatment of ovariectomized rodents is known to affect the morphology of dendritic spines and produce behavioral and cognitive effects. Kalirin-7 (Kal7), a postsynaptic density (PSD)-localized Rho-guanine nucleotide exchange factor, is important for dendritic spine formation and stability. Male Kal7 knockout [Kal7(KO)] mice exhibit a number of abnormal behavioral and biochemical phenotypes. Given that chronic 17β-estradiol (E2) replacement of ovariectomized rats enhanced Kal7 expression in the hippocampus and primary hippocampal cultures, we assessed the behavioral and biochemical effects of chronic E2 treatment of ovariectomized female wild-type and Kal7(KO) mice. Both intact and ovariectomized Kal7(KO) female mice exhibited decreased anxiety-like behavior compared with the corresponding wild type in the elevated zero maze and were unaffected by E2 treatment. Chronic E2 decreased locomotor activity in the open field and enhanced performance in a passive-avoidance fear conditioning task, which were both unaffected by genotype. Kal7(KO) female mice engaged in significantly more object exploration, both familiar and novel, than did wild-type females. E2 enhanced the acute locomotor response to cocaine, with no significant effect of genotype. Similar to Kal7(KO) males, Kal7(KO) females had decreased levels of N-methyl-d-aspartate receptor 2B in hippocampal PSD fractions with no effect of E2 treatment. The differing behavioral effects of Kal7 ablation in female and male mice may offer insight into the molecular underpinnings of these differences.
已证实，对去卵巢啮齿动物进行雌二醇处理会影响树突棘的形态，并产生行为和认知影响。Kalirin-7（Kal7）是一种突触后密度（PSD）定位的Rho 鸟嘌呤核苷酸交换因子，对于树突棘的形成和稳定性很重要。雄性 Kal7 敲除[Kal7（KO）]小鼠表现出多种异常的行为和生化表型。鉴于慢性 17β-雌二醇（E2）替代去卵巢大鼠增强了海马体和原代海马培养物中 Kal7 的表达，我们评估了慢性 E2 处理去卵巢雌性野生型和 Kal7（KO）小鼠的行为和生化影响。与相应的野生型相比，完整的和去卵巢的 Kal7（KO）雌性小鼠在高架零迷宫中表现出焦虑样行为减少，并且不受 E2 处理的影响。慢性 E2 降低了开阔场中的运动活性，并增强了被动回避恐惧条件反射任务的表现，而基因型不受影响。Kal7（KO）雌性小鼠比野生型雌性小鼠进行了更多的物体探索，无论是熟悉的还是新的。E2 增强了可卡因的急性运动反应，而基因型没有显着影响。与 Kal7（KO）雄性相似，Kal7（KO）雌性小鼠海马体 PSD 分数中的 N-甲基-D-天冬氨酸受体 2B 水平降低，E2 处理无影响。Kal7 消融在雌性和雄性小鼠中的不同行为影响可能为这些差异的分子基础提供了深入了解。
