岛叶中蛋白激酶M zeta在恒河猴吗啡诱导的条件性位置偏好中的作用
文献类型：学位论文
| 作者 | 张洋 |
| 学位类别 | 硕士 |
| 答辩日期 | 2015-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 王建红 |
| 关键词 | 恒河猴 吗啡CPP PKMζ ZIP |
| 其他题名 | The protein kinase M zeta in insula on morphine conditioned place preference in rhesus |
| 中文摘要 | 蛋白激酶M zeta（Protein Kinase Mζ PKMζ）是近年发现的与长时记忆保持相关蛋白质。它具有持续活性，可促进α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors AMPA）不断插入突触后膜位点，使突触后膜所在的神经元去极化，行为水平表现为长时记忆的保持。药物成瘾是一种特殊而强烈的长时记忆，在药物戒除后，与成瘾药物相关的线索记忆可以长期保持，当再次暴露在这些线索下时可能会导致药瘾复发。本试验使用的行为范式——吗啡诱导的条件性位置偏好(Condition Place Perference CPP，可使实验对象在特定环境内形成吗啡相关学习记忆，通过分析吗啡摄入室内的偏好值来判断成瘾记忆的保持情况。岛叶（Insula）具有执行躯体感觉信息和内脏信息整合的功能，岛叶可能参与生理渴求成瘾药物到意识渴求的转变的过程，当前的研究发现人类岛叶与尼古丁渴求有关。本实验利用恒河猴为实验对象建立吗啡CPP，并向岛叶前部（AI）和岛叶后部（PI）分别注射PKMζ抑制剂——zeta抑制多肽（zeta inhibitory peptide ZIP），发现ZIP显著降低吗啡CPP表达。通过蛋白印迹实验对长时记忆相关的PKMζ、PKCι和GluA2的蛋白质表达量进行分析发现：CPP-ZIP组后岛叶（PI）中GluA2蛋白表达量相比食物CPP组有显著的提高；海马（Hip）中PKMζ相比对照组有显著的提高；伏隔核（NAc）中PKCι和GluA2的蛋白质表达量相比空白对照组有上升趋势；杏仁核（Amy）中PKMζ和GluA2的蛋白质表达量较空白对照组有上升趋势；岛叶中PKMζ或PKCι在吗啡CPP建立期、吗啡CPP建立后ZIP注射干预期表达量变化不显著。这表明PKMζ可能是海马区保持长时空间位置记忆的关键分子，岛叶可能是影响吗啡成瘾长期记忆的重要脑区，但吗啡成瘾长期记忆的保持在岛叶中的关键分子可能不是PKMζ或PKCι，不同脑区长时记忆保持的分子机制不同。 |
| 英文摘要 | Protein kinase M zeta (PKMζ) is associated with maintaining long-term memory . Because of its special molecular structure, PKMzeta has the autonomous activity to maintained LTP and long-term memory. It can promote α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors (AMPA) inserted in sites of postsynaptic membrane constantly. It performs LTP is sustained in the neuron level, and it performs long-term memory maintenance in the behavioral level . As a special kind of memory, drug addiction catches researchers’ attention. After the withdrawal of an addictive drug, the drug addiction-related cues can maintain long-term memory when exposed to these cues may again cause addiction relapse. In this study, we used rhesus monkeys morphine conditioned place preference (CPP) as behavioral paradigm to study drug addiction by analyzing the preference to morphine chamber . Insula may be involved in integrating the physiological drug craving and changing it to conscious addiction. Current study found that insula may effect nicotine addiction in human .In this study, we injected ZIP to macaques’ insula on after CPP, and reduced the preference significantly. By western blot, we found: GluA2 protein expression of CPP-ZIP group significantly improved compared to food CPP group; PKMζ in hippocampus improved significantly compared to the control group; protein expression levels of PKCι and GluA2 in nucleus accumbens is the upward trend; in amygdala, protein expression of GluA2 and PKMζ is an upward trend; in insula, there is no significant change in expression levels of PKMζ and PKCι during morphine CPP and injection ZIP. This result suggests that insula may affect morphine addiction, but PKMζ and PKCι may not be key that maintaining long-term memory in the insular cortex. PKMζ in hippocampus maintains the spatial long-term memory. Different area in brain may have different molecular mechanisms of maintaining memory. |
| 语种 | 中文 |
| 源URL | [http://159.226.149.26:8080/handle/152453/10129]  |
| 专题 | 昆明动物研究所_神经系统编码 |
| 推荐引用方式 GB/T 7714 | 张洋. 岛叶中蛋白激酶M zeta在恒河猴吗啡诱导的条件性位置偏好中的作用[D]. 北京. 中国科学院研究生院. 2015. |
入库方式： OAI收割
来源：昆明动物研究所
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