Neuroscience Program, Tulane University, New Orleans, LA 70118, United States.
Neurobiol Learn Mem. 2012 Oct;98(3):284-90. doi: 10.1016/j.nlm.2012.09.006. Epub 2012 Sep 22.
Actin rearrangement, the polymerization of globular actin (G-actin) to filamentous actin, causes morphological changes in dendritic spines and is hypothesized to be a substrate of learning and memory. The ovarian hormone estradiol promotes hippocampal actin rearrangement and enhances performance on hippocampus-dependent tasks, including object placement memory. The goals of the current study were to determine a role for actin rearrangement and its regulatory pathway in object placement memory in female rats and to determine if estradiol impacts actin rearrangement in ovariectomized rats during the performance of the task. In an initial experiment, young adult Long-Evans rats were ovariectomized and implanted with capsules containing either cholesterol vehicle or estradiol. Bilateral intrahippocampal infusions of aCSF vehicle or the actin rearrangement inhibitor, latrunculin A, were administered 15 min prior to initiation of the object placement task. Latrunculin A dose-dependently impaired object placement memory. Estradiol had no impact on the ability of latrunculin A to affect performance. In a second experiment, rats were ovariectomized and received implants containing cholesterol or estradiol. Half of each hormone treatment group was exposed to the object placement memory task and half underwent control procedures. Immediately following completion of behavior, rats were euthanized and hippocampi removed. Western blotting was used to measure hippocampal levels of phosphorylated and total levels of a regulator of actin polymerization, the actin depolymerization factor cofilin. Exposure to the object placement memory task resulted in significant increases in phosphorylated levels of cofilin. Estradiol treatment had no impact on protein levels. These data support a role for hippocampal actin rearrangement and its regulatory proteins in object placement memory in female rats and suggest that chronic estradiol treatment does not impact hippocampal actin arrangement.
肌动蛋白重排，即球状肌动蛋白（G-actin）聚合形成丝状肌动蛋白，导致树突棘的形态变化，被假设为学习和记忆的底物。卵巢激素雌二醇促进海马体的肌动蛋白重排，并增强了与海马体相关的任务的表现，包括物体放置记忆。本研究的目的是确定肌动蛋白重排及其调节途径在雌性大鼠物体放置记忆中的作用，并确定雌二醇是否会影响去卵巢大鼠在执行任务期间的肌动蛋白重排。在初步实验中，年轻的成年 Long-Evans 大鼠被去卵巢，并植入含有胆固醇载体或雌二醇的胶囊。在开始物体放置任务之前 15 分钟，双侧海马内注射 aCSF 载体或肌动蛋白重排抑制剂拉曲库林 A。拉曲库林 A 呈剂量依赖性地损害物体放置记忆。雌二醇对拉曲库林 A 影响表现的能力没有影响。在第二个实验中，大鼠被去卵巢并接受含有胆固醇或雌二醇的植入物。每个激素处理组的一半接受物体放置记忆任务，另一半接受对照程序。在完成行为后，大鼠立即被安乐死并取出海马体。使用 Western 印迹法测量海马体中肌动蛋白聚合调节剂、肌动蛋白解聚因子丝切蛋白的磷酸化和总水平。暴露于物体放置记忆任务导致丝切蛋白的磷酸化水平显著增加。雌二醇处理对蛋白水平没有影响。这些数据支持海马体肌动蛋白重排及其调节蛋白在雌性大鼠物体放置记忆中的作用，并表明慢性雌二醇处理不会影响海马体的肌动蛋白排列。
