非选择性阳离子通道在GRP调节海马神经通路中的作用及其机制研究

项目名称： 非选择性阳离子通道在GRP调节海马神经通路中的作用及其机制研究

项目编号： No.31300923

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 姚扬

作者单位： 天津市第一中心医院

项目金额： 22万元

中文摘要： 多种神经系统疾病可导致认知功能障碍。胃泌素释放肽（Gastrin-releasing peptide，GRP)与情绪记忆功能相关，而其在海马区的作用及其机制尚不明确。我们的前期工作发现，GRP可以兴奋丘脑内神经元，其机制是激活非选择性阳离子通道（NSCC）。在预实验中发现GRP受体激动剂可以改善缺血大鼠的空间学习记忆能力及海马突触可塑性。据此我们推测"GRP能够通过激活NSCC来调节海马神经元及神经通路，进而提高动物的认知功能"。 本项目拟采用慢病毒感染、膜片钳、水迷宫、场电位记录及免疫组织化学等技术，首先观察GRP对海马神经元电生理特性的影响，研究其对海马神经通路的作用机制，并观察对血管性痴呆小鼠学习记忆的影响。从细胞-组织-整体层次证明我们的假说。本研究具有重要理论意义和应用价值，为研究GRP对学习记忆的影响及其机制提供理论依据，并为认知功能障碍的防治提供新思路和药物作用的新靶点。

中文关键词： 胃泌素释放肽；非选择性阳离子通道；;海马神经通路；学习记忆；电生理学

英文摘要： Cognitive disorder can be caused by a number of neurological diseases. Gastrin-releasing peptide (GRP) is a mammalian neuropeptide that regulated brain function of memory and behavior.The mechanism of its effects on the hippocampus are still unclear. Our previous work indicated that GRP could excite neurons in the thalamus, and its excitation effects were connected with the activation of non-selective cation channel(NSCC). Our preliminary experiment showed that GRP receptor agonist can attenuate the spatial memory and synaptic placisity deficits in rats with vascular dementia (VD). Base on those findings, we propose that "GRP can, through activating NSCC, modulate hippocampal neuronal network and improve the cognitive ability".In this proposal, by using engineered virus inoculation, patch-clamp , Morris water maze, field potential recording and immuno-histological technique, we plan to first observe the effetcs of GRP on the electro-property of the hippocampal neurons, study its effects on the hippocampal neuronal network and examine its effects on learning and memory deficits in VD mice. We plan to prove our hypothesis in cell-tissue-in vivo animal levels. This study can be of great significance in both theoretical and applied research, it can provide further evidence for studying the effects of GRP on learnnin

英文关键词： Gastrin-releasing peptide；non-selective cation channel；hippocampal neuronal network；learning and memory；electro-physiology