Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning
Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning
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DOI：
10.1016/s0306-4522(03)00597-9
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Sandi, C
中科院分区：
文献类型：
--
作者：
Cambon, K;Venero, C;Sandi, C
神经细胞粘附分子（NCAM）在突触可塑性和记忆形成中起关键作用。我们最近开发了一种合成肽，称为C3 d，其通过结合到NCAM的细胞外部分中的第一个N-末端免疫球蛋白样（IG）模块，已被证明在体外促进神经突生长和突触形成，并在体内干扰大鼠的被动回避记忆。在这项研究中，我们调查了C3 d的i. c. v.管理，无论是5.5小时后或2天前的培训，可以有效地调节的强度，在情绪记忆的厌恶的情况下，建立到一个长期的记忆。在背景恐惧条件反射任务中训练的成年雄性Wistar大鼠中评价肽的作用。结果表明，C3 d显着降低了随后的长期保留的条件性恐惧反应时，管理5.5小时后的培训，所示的保留测试进行2-3和7天后的培训。然而，当在训练前2天注射时，这种治疗未能影响该任务的条件反射。其他实验表明，C3 d不影响动物的情绪或运动行为，当在开放领域的任务进行测试。此外，海马微管相关蛋白2（MAP 2），突触素和NCAM的水平被发现不变时，通过酶联免疫吸附试验在粗突触体制剂肽i. c. v.注射后2天进行评价。因此，训练后注射这种合成肽可以有效地减弱背景恐惧条件反射记忆的强度，同时不影响新记忆的获得。除了进一步支持NCAM在记忆巩固中起关键作用的观点外，目前的研究结果表明，NCAM IgI模块是开发治疗药物的潜在目标，这些药物能够减少暴露于强烈压力体验引起的认知影响。(C)2003年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days post-training. However, this treatment failed to influence conditioning for this task when injected 2 days pre-training. Additional experiments showed that C3d did not influence the emotional or locomotor behaviour of the animals, when tested in the open field task. Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the cognitive impact induced by exposure to intensive stress experiences. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.