Evidence that integrins contribute to multiple stages in the consolidation of long term potentiation in rat hippocampus
Evidence that integrins contribute to multiple stages in the consolidation of long term potentiation in rat hippocampus
复制标题
DOI：
10.1016/s0306-4522(01)00173-7
复制
发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Lynch, G
中科院分区：
文献类型：
--
作者：
Chun, D;Gall, CM;Lynch, G
三个结构不同的拮抗剂组被用来测试的假设，整合素粘附受体巩固（稳定）在大鼠海马的Schaffer侧支的长时程增强发挥重要作用。在同一海马切片的CAI放射层内，对拮抗剂处理与对照部位的增强百分比进行了比较。针对纤连蛋白受体α 5亚基的功能阻断抗体对基线反应或初始增强没有影响，但在45分钟后，相对于切片内对照长时程增强，导致> 30%的减少。更大的减少记录在单独的实验中，持续4小时后，诱导增强。α（v）和α 2亚单位抗体没有可靠地影响增强的稳定性。偏好β 1整联蛋白的拮抗剂肽产生与α 5抗体所见类型的缓慢发展的下降。一种环肽拮抗剂在诱导后10分钟内减少了增强作用，并在45分钟内减少了近40%。两种去整合素（能有效阻断整合素的蛇毒）在防止长时程增强作用的巩固方面非常有效：echistatin减少了> 70%的增强作用，而triflavin减少了50%。echistatin的抑制作用是浓度依赖性的，在诱导后处理获得，并且比抗体的作用快得多。增强的快速下降是特别明显的，当两个disintegrin应用在一起。这些结果表明，海马纤连蛋白受体（α 5/β 1整合素）作出重要贡献的一个缓慢发展阶段的长期增强巩固。他们还表明，其他整合素是关键方面的巩固发生在诱导后的头几分钟。((C)2001年IBRO。由Elsevier Science Ltd.出版，版权所有。
Three structurally distinct groups of antagonists were used to test the hypothesis that integrin adhesion receptors play an essential role in consolidating (stabilizing) long term potentiation of the Schaffer collaterals in rat hippocampus. Comparisons were made of percent potentiation at antagonist-treated versus control sites within CAI stratum radiatum of the same hippocampal slice. Function blocking antibodies against the alpha5 subunit of the fibronectin receptor had no effect on baseline responses or initial potentiation but resulted in a > 30% reduction, relative to within-slice control long term potentiation, 45 min later. Larger reductions were recorded in separate experiments continued for 4 h after the induction of potentiation. Alpha(v) and alpha2 subunit antibodies did not reliably affect the stabilization of potentiation. An antagonist peptide with preference for beta1 integrins produced a slowly developing decline of the type seen with alpha5 antibodies. A cyclic peptide antagonist reduced potentiation within 10 min of induction and caused an almost 40% decrease over 45 min. Two disintegrins (snake toxins that potently block integrins) were very effective in preventing the consolidation of long term potentiation: echistatin reduced potentiation by > 70%, while triflavin caused similar to 50% decrease. The suppressing effects of echistatin were concentration-dependent, obtained with treatment after induction, and much more rapid than the effects of antibodies. Rapid declines in potentiation were particularly evident when the two disintegrins were applied together.These results indicate that hippocampal fibronectin receptors (alpha5/beta1 integrin) contribute importantly to a slowly developing phase of long term potentiation consolidation. They also suggest that other integrins are critical to aspects of consolidation occurring in the first few minutes after induction. ((C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.