McLaughlin Katie J, Bimonte-Nelson Heather, Neisewander Janet L, Conrad Cheryl D
Department of Psychology, Arizona State University, Tempe, AZ, 85287-1104, USA.
Horm Behav. 2008 Aug;54(3):386-95. doi: 10.1016/j.yhbeh.2008.04.010. Epub 2008 May 9.
Two pulses of 17beta-estradiol (10 microg) are commonly used to increase hippocampal CA1 apical dendritic spine density and alter spatial performance in ovariectomized (OVX) female rats, but rarely are the measures combined. The goal of this study was to use this two-pulse injection protocol repeatedly with intervening wash-out periods in the same rats to: 1) measure spatial ability using different tasks that require hippocampal function and 2) determine whether ovarian hormone depletion for an extended 10-week period reduces 17beta-estradiol's effectiveness in elevating CA1 apical dendritic spine density. Results showed that two injections of 10 microg 17beta-estradiol (72 and 48 h prior to testing and timed to maximize CA1 apical spine density at behavioral assessment) corresponded to improved spatial memory performance on object placement. In contrast, two injections of 5 microg 17beta-estradiol facilitated spatial learning on the water maze compared to rats given two injections of 10 microg 17beta-estradiol or the sesame oil vehicle. Neither 17beta-estradiol dose altered Y-maze performance. As expected, the intermittent two-pulse injection protocol increased CA1 apical spine density, but 10 weeks of OVX without estradiol treatment decreased the effectiveness of 10 microg 17beta-estradiol to increase CA1 apical spine density. Moreover, two pulses of 5 microg 17beta-estradiol injected intermittently failed to alter CA1 apical spine density and decreased basal spine density. These results demonstrate that extended time without ovarian hormones reduces 17beta-estradiol's effectiveness to increase CA1 apical spine density. Collectively, these findings highlight the complex interactions among estradiol, CA1 spine density/morphology, and task requirements, all of which contribute to behavioral outcomes.
通常使用两脉冲的17β-雌二醇（10微克）来增加去卵巢（OVX）雌性大鼠海马CA1区顶端树突棘密度并改变其空间行为表现，但很少将这些测量方法结合起来。本研究的目的是在同一批大鼠中重复使用这种两脉冲注射方案，并设置中间洗脱期，以：1）使用需要海马功能的不同任务来测量空间能力；2）确定长达10周的卵巢激素缺失是否会降低17β-雌二醇提高CA1区顶端树突棘密度的有效性。结果显示，两次注射10微克17β-雌二醇（测试前72小时和48小时，并在行为评估时使CA1区顶端棘密度最大化）对应于物体放置任务中空间记忆表现的改善。相比之下，与接受两次注射10微克17β-雌二醇或芝麻油载体的大鼠相比，两次注射5微克17β-雌二醇促进了水迷宫中的空间学习。两种剂量的17β-雌二醇均未改变Y迷宫表现。正如预期的那样，间歇性两脉冲注射方案增加了CA1区顶端棘密度，但10周的去卵巢且未接受雌二醇治疗降低了10微克17β-雌二醇增加CA1区顶端棘密度的有效性。此外，间歇性注射两次5微克17β-雌二醇未能改变CA1区顶端棘密度，并降低了基础棘密度。这些结果表明，长时间缺乏卵巢激素会降低17β-雌二醇增加CA1区顶端棘密度的有效性。总的来说，这些发现突出了雌二醇、CA1区棘密度/形态和任务要求之间复杂的相互作用，所有这些都对行为结果有影响。
