Jafarinejad-Farsangi Saeideh, Farazmand Ali, Rezayof Ameneh, Darbandi Niloufar
Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
Iran J Pharm Res. 2015 Spring;14(2):591-602.
Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity.
吗啡对学习和记忆过程的影响众所周知，依赖于海马体中的突触可塑性。虽然海马体在吗啡诱导的失忆和状态依赖学习中的作用已经明确，但这些过程背后的生化和分子机制却知之甚少。本研究旨在调查在被动回避任务学习过程中，给予吗啡是否会改变大鼠海马体蛋白质的表达水平。采用一步通过式被动回避任务来评估记忆保持情况。为了识别由吗啡诱导的复杂蛋白质表达模式，我们通过二维凝胶电泳和串联质谱（MS和MS/MS）比较了吗啡诱导失忆或状态依赖学习情况下大鼠海马体蛋白质组。训练后给予吗啡会缩短一步通过潜伏期。测试前给予吗啡会诱导在训练后吗啡影响下获得的记忆的状态依赖检索。在海马体中，共鉴定出18种蛋白质，其MASCOT（软件构建操作与测试模块化方法）得分在95%置信水平内。其中，5种海马体蛋白质在吗啡诱导的失忆中发生改变，10种蛋白质在接受训练后和测试前给予吗啡的动物海马体中被发现发生变化。这些蛋白质在细胞骨架结构、细胞代谢、神经递质分泌和神经保护方面具有已知功能。研究结果表明，吗啡对被动回避学习中记忆形成的影响在海马体蛋白质组水平上具有形态学相关性。此外，我们的蛋白质组学筛选表明，吗啡通过调节神经元可塑性诱导记忆损伤和状态依赖学习。
