淀粉样蛋白对海马长时程增强的影响-ACTAPS.pdfVIP

生理学报 Acta Physiologica Sinica, December 25, 2010, 62(6): 479-488 479 综 述 - 淀粉样蛋白对海马长时程增强的影响 张俊芳，杨东，祁金顺* 山西医科大学生理学系，细胞生理学省部共建教育部重点实验室，太原 030001 摘 要：- 淀粉样蛋白(amyloid -protein, A)在脑内沉积形成的老年斑是阿尔茨海默病(Alzheimer’s disease, AD) 的一个主要 病理特征。然而，目前研究表明，在AD 出现神经变性前的早期记忆功能障碍中，可溶性A  已经发挥了重要作用。可 溶性A引起认知功能下降的机制目前尚不清楚。海马长时程增强(long-term potentiation, LTP)是反映突触可塑性的重要指 标，被认为与学习和记忆的形成有关。关于A 影响海马LTP 的研究报道，尤其是利用转基因动物取得的研究成果，为 解释AD 患者出现的学习记忆功能障碍提供了有力的实验证据。本文结合近年来对AD 进行的诸多基础性研究，扼要介绍 了A 尤其是可溶性A 及其活性片段对海马LTP 的影响，并讨论了A 抑制海马LTP 的可能机制。 关键词：阿尔茨海默病；- 淀粉样蛋白；长时程增强；海马 中图分类号：R338 Effects of amyloid -protein on hippocampal long-term potentiation ZHANG Jun-Fang, YANG Dong, QI Jin-Shun* Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China Abstract: The accumulation of amyloid -protein (A) plaques is identified as a major pathological feature of Alzheimer’s disease (AD). Recent studies show that soluble species of A are involved in the early memory dysfunction long before neurodegenerative changes. However, the mechanism underlying the neurotoxicity of soluble A is still unclear. Long-term potentiation (LTP) has been thought as an important cellular model of synaptic plasticity for many years. The studies on the hippocampal LTP and A, especially those using AD transgenic models, provided more evidence for the A-induced dysfunction of learning and memory. Based on the recent researches on AD, this article reviewed the effects of A, especially soluble A and its active fragments, on the hippocampal LTP. The possible mechanisms by which A impairs hippocampal LTP are also discussed. Key words: Alzheimer’s disease; amyloid -protein; long-term potentiation; hippocampus 1 引言 成分为- 淀粉样蛋白(amyloid -protein, A) ；AD 阿尔茨海默病(Alzheimer’s disease, AD)是一种以 患者的脑细胞内还具有典型的神经原纤维缠结 进行性认