创伤性场景恐惧记忆遗忘机制的研究

项目名称： 创伤性场景恐惧记忆遗忘机制的研究

项目编号： No.81460216

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 蒋丽珠

作者单位： 大理大学

项目金额： 48万元

中文摘要： 创伤后应激障碍（PTSD）以创伤性恐惧记忆的病理性增强、延迟或不能遗忘为核心症状。但关于创伤性恐惧记忆遗忘的机理几乎一无所知。研究表明记忆的不能遗忘现象可能与5-HT系统和Rac1下游分子actin有关。我们前期研究发现海马Rac1调控着大鼠场景恐惧记忆的遗忘，而5-HT系统与PTSD的生理病理密切相关。因此，我们推测5-HT系统可能调控海马Rac1的活性并参与创伤性场景恐惧记忆的遗忘。本课题将研究：①场景条件恐惧学习后大鼠背侧中缝核、海马等脑区5-HT1A、5-HT1B、5-HT2A受体、5-HT转运及 F-actin的表达；②干预条件恐惧学习所至5-HT1A、5-HT1B、5-HT2A、5-HT转运体及F-actin的变化，检测其变化与海马Rac1活性及动物场景恐惧记忆遗忘的关系。③PTSD病人外周血Rac1 mRNA的变化。实验结果将为PTSD的治疗提供新的途径。

中文关键词： 创伤后应激障碍；背侧中缝核；海马；遗忘；Rac1;5-HT受体

英文摘要： Posttraumatic stress disorder (PTSD) is a mental disorder that may develop after a person is exposed to traumatic events, which is characterized by hypermnesia or cannot forgetting. However, little is about the forgetting of traumatic memory. Previous researches indicate the phenomena of unforgetting may be involved in serotonin and actin. We found Rac1 activity in hippocampus regulated the forgetting of contextual fear memory in rat，previous researches show 5-HT1A, 5-HT1B, 5-HT2A and serotonin transporter(SERT) are involved in to fear memory. Thus, we hypothesise 5-HT1A, 5-HT1B, 5-HT2A and SERT are involved in regulation of Rac1 activity in the hippocampus and the forgetting of contextual fear memory, Rac1 signal pathway may be the last pathway of PTSD. Here we will investigate ① the effects of contextual fear conditioning on the level of 5-HT1A, 5-HT1B, 5-HT2A, SERT and F-actin in the dorsal raphe nucleus(DRN) and hippocampus. ② the effect of promotion or inhibition of 5-HT1A, 5-HT1B, 5-HT2A and SERT in DRN or hippocampus on hippcampal Rac1 activity and contextual fear memory in rats.③ the level of serum Rac1 mRNA in PTSD patients. These data will be important for a better understanding of the forgetting mechanisms of traumatic memory and provide potential target to theatment of PTSD.

英文关键词： PTSD;DRN;hippocampus;forgetting;Rac1;5-HT receptors