Effects of an exogenous β-amyloid peptide on retention for spatial learning

Michael P. McDonald , Eric E. Dahl , J. Bruce Overmier , Patrick Mantyh , James Cleary
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引用次数: 79

Abstract

Three experiments assessed the effects of β-amyloid 1–40 (βA4) on spatial learning in Sprague-Dawley rats. In Experiment 1, rats were trained on a signaled footshock avoidance in a Y-maze. Rats received a single injection of βA4 or vehicle in both sides of the hippocampus immediately after the fifth trial. The βA4 group took significantly longer than the vehicle group to learn to avoid the shock when trained to criterion 1 week later, suggesting a detrimental effect of βA4 on memory consolidation. Experiment 2 used a food reinforcer rather than shock relief under procedures similar to Experiment 1. Again, the βA4 group took longer to learn the maze to criterion. This shows that the effect in Experiment 1 was not specific to shock-maintained learning. In Experiment 3, rats were trained to retrieve a food pellet from each arm of an eight-arm radial maze. After training to criterion, β4 or vehicle was administered intrahippocampally 30 min before the daily session for 26 sessions. There were no acute or chronic effects of βA4 injection on radial maze performance, and no aggregation of βA4 or significant necrosis was observed upon postmortem histological analysis. These experiments suggest that single injections of βA4 impair memory consolidation, but repeated injections of βA4 over an extended period do not affect well-learned behavior.

外源性β-淀粉样肽对空间学习记忆的影响
三个实验评估了β-淀粉样蛋白1-40 (βA4)对Sprague-Dawley大鼠空间学习的影响。在实验1中,大鼠在y形迷宫中进行了避足信号训练。大鼠在第五次试验后立即接受海马两侧单次注射βA4或载体。βA4组在1周后达到标准时学习避免电击的时间明显长于载具组,提示βA4对记忆巩固有不利影响。实验2采用与实验1类似的程序,使用食品强化剂而不是减震剂。同样,βA4组花了更长的时间来学习迷宫到标准。这表明实验1中的效果并不局限于休克维持学习。在实验3中,大鼠被训练从八臂放射状迷宫的每只手臂中取回食物颗粒。训练达到标准后,在每日训练前30分钟海马内给予β4或载体,共26次。注射βA4对小鼠径向迷宫表现无急性或慢性影响,死后组织学分析未见βA4聚集或明显坏死。这些实验表明,单次注射βA4会损害记忆巩固,但长时间反复注射βA4不会影响已习得的行为。
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