AMPK/SIRT1 信号通路调控线粒体能量代谢功能对焦虑样行为的 影响及机制探讨
文献类型：学位论文
| 作者 | 赵安然 |
| 答辩日期 | 2022-06 |
| 文献子类 | 硕士 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 郭建友 |
| 关键词 | 焦虑症 线粒体功能 能量代谢 AMPK/SIRT1 通路 |
| 学位名称 | 理学硕士 |
| 学位专业 | 健康心理学 |
| 其他题名 | Effects of AMPK/SIRT1 signaling pathway on mitochondrial energy metabolism and its mechanism on anxiety-like behavior |
| 中文摘要 | Anxiety disorder as a very common mental disease in today's society, its etiology is not clear, its pathogenic factors may include genetics, personality characteristics, cognitive patterns, external events stimulation, etc.. Clinical treatment of anxiety disorders is mainly cognitive behavioral therapy and drug therapy. However, even after treatment with multiple anti-anxiety drugs, nearly 40 percent of patients had no or minimal response. Therefore, we need to conduct in-depth research on the basic physiological mechanism of anxiety disorders, so as to find therapeutic targets for its basic mechanism. With the further study of mitochondrial oxidative phosphorylation, more and more evidences indicate that mitochondrial dysfunction is involved in the pathological process of anxiety disorders. In the new study, the researchers propose a treatment mechanism involving mitochondria. Studies have shown that mitochondrial function is altered in high-anxiety animals, and that the use of compounds targeting mitochondria can improve anxiety-like symptoms. Therefore, it is necessary to study the biological essence and mechanism of anxiety disorder from the perspective of abnormal mitochondrial energy metabolism, and explore the regulatory mechanism of mitochondrial function. A large number of studies have revealed that the Adenosine 5 '-Monophosphate-Activated protein kinase/Sirtuin1 (AMPK/SIRT1) pathway affects mitochondrial function by regulating mitochondrial biosynthesis. Therefore, this study intends to establish an anxiety model in rats by using uncertain empty bottle drinking stress, and observe the changes in mitochondrial energy metabolism mediated by AMPK/SIRT1 pathway in amygdala and medial prefrontal cortex, so as to reveal the anti-anxiety mechanism of this pathway. In this study, the following three studies were carried out: Study 1 used the uncertain empty bottle drinking water stress model to establish the animal anxiety model, and the elevated Cross maze (EPM) and open field (OFT) tests were used to investigate the anxiety level of the control group and the model group on the 7th, 14th and 21st days of stress. Study 2 Transmission electron microscopy was used to observe the morphological changes of mitochondria in amygdala and medial prefrontal cortex. In study 3, the changes in mitochondrial energy metabolism mediated by AMPK/SIRT1 pathway in amygdala and medial prefrontal cortex were observed, and the expression levels of AMPK/SIRT1 pathway-related proteins were determined to clarify the possible relationship between AMPK/SIRT1 pathway-mediated mitochondrial energy metabolism abnormalities and the pathogenesis of anxiety disorders. The results showed that the mitochondrial structure of model group rats was damaged, the mitochondrial energy level was decreased, and the expression level of AMPK/SIRT1 pathway related protein molecules was significantly decreased. These results suggest that mitochondrial energy metabolism is related to anxiety-like behavior, and AMPK/SIRT1 pathway is involved in the corresponding anxiety pathological process. Studies have shown that AMPK/SIRT1 pathway mediated mitochondrial energy metabolism disorder is the main mechanism of anxiety disorders, providing a new theoretical basis for anxiety related research. |
| 英文摘要 | 焦虑症作为一种当今社会十分常见的精神疾病，目前其病因尚不明确，其致病 因素可能包括遗传、个性特点、认知模式、外界事件刺激等。临床上对焦虑症的治 疗手段主要是认知行为疗法以及药物疗法。然而，即使在使用多种抗焦虑药物进行 治疗之后，仍有近 40%的患者治疗无效果，或者效果极微弱。因此，我们需要对焦 虑症的基础生理机制进行深入研究，以便找到针对其基础机制的治疗靶点。 随着对线粒体氧化磷酸化过程的深入研究，越来越多的证据表明线粒体功能异 常参与了焦虑症的病理过程。在新的研究中，研究人员提出涉及线粒体的治疗机制。 研究证明高焦虑的动物线粒体功能会发生改变，且使用靶向线粒体的化合物可以改 善焦虑样症状。因此有必要从线粒体能量代谢异常角度研究焦虑症部分生物学实质 和 作 用 机 制 ， 并 探 索 线 粒 体 功 能 的 调 控 机 制 。 大 量 研 究 揭 示 Adenosine 5‘-monophosphate-activated protein kinase/Sirtuin1（AMPK/SIRT1）通路通过调控线 粒体生物合成影响线粒体功能，故本研究拟采用不确定性空瓶饮水应激建立大鼠焦 虑模型，观察杏仁核、内侧前额叶皮质 AMPK/SIRT1 通路介导的线粒体能量代谢 变化，以揭示该通路的抗焦虑机制。 本课题进行了以下三个研究：研究 1 使用不确定空瓶饮水应激模型建立动物焦 虑模型，在应激第 7、14、21 天采用高架十字迷宫（EPM）和旷场（OFT）测试考 察其焦虑水平，观察控制组和模型组的焦虑情况。研究 2 利用透射电镜观察动物杏 仁核及内侧前额叶皮质的线粒体形态结构的变化。研究 3 探讨相应蛋白通路变化情 况，观察动物杏仁核、内侧前额叶皮质 AMPK/SIRT1 通路介导的线粒体能量代谢 变化，测定 AMPK/SIRT1 通路相关蛋白表达水平，以阐明 AMPK/SIRT1 通路介导 的线粒体能量代谢异常与焦虑症发病机制的可能关系。 研究结果显示不确定空瓶应激诱导的焦虑样行为变化呈时间依赖性，在 21 天 差异最显著；行为学的改变伴随焦虑模型组大鼠线粒体结构破坏，线粒体能量水平 降低，AMPK/SIRT1 通路相关蛋白分子的表达水平显著下降。该结果提示线粒体能 量代谢水平与焦虑样行为相关，AMPK/SIRT1 通路参与相应焦虑病理过程。研究表 明 AMPK/SIRT1 通路介导的线粒体能量代谢失调是焦虑症发病的关键机制，为焦 虑症相关研究提供新的理论依据。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/43145]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 赵安然. AMPK/SIRT1 信号通路调控线粒体能量代谢功能对焦虑样行为的 影响及机制探讨[D]. 中国科学院心理研究所. 中国科学院大学. 2022. |
入库方式： OAI收割
来源：心理研究所
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