蛋白激酶C对焦虑样行为小鼠前边缘皮层突触结构和功能变化的作用研究
发布时间：2019-01-26 09:15
【摘要】：焦虑症是最为广泛流行的精神失调症之一,前额叶皮层和杏仁核的γ-氨基丁酸、五羟色胺和谷氨酸能系统的功能缺陷被认为与焦虑症的发病机制有关。但是在这些区域,细胞网络和突触的病理性改变及涉及的机制目前尚不清楚。 长久以来的观点认为五羟色胺能和γ-氨基丁酸能的突触功能缺陷与焦虑症相关。选择性的五羟色胺重摄取抑制剂和γ-氨基丁酸受体增强剂被用来作为抗焦虑药物使用。但是由于副作用众多,这些药物的治疗效果需要被重新评估。最近的结果显示,谷氨酸能系统也与焦虑症有关,离子型谷氨酸受体拮抗剂被认为是潜在的抗焦虑药物。从这个意义上讲,离子型谷氨酸受体激动剂理论上可以引起小鼠的焦虑样行为。本文阐述了离子型谷氨酸受体激动剂在焦虑症病理性改变中的作用及其相关机制,为焦虑症的治疗提供了潜在靶点。 我们发现,离子型谷氨酸受体激活剂海人藻酸(Kainic Acid, KA)能够引起小鼠的焦虑样行为,并且前边缘皮层兴奋性神经元兴奋性突触的功能和结构都发生了病理性改变,使用蛋白激酶C选择性拮抗剂白屈菜红碱(Chelerythrine Chloride, CHE)能够阻断杂交小鼠因为海人藻酸引起的行为、突触功能及突触结构的变化。以上研究阐明了离子型谷氨酸受体激动剂在焦虑症的发病及病理性功能和结构改变的过程中的作用,而蛋白激酶C (Protein Kinase C, PKC)在此扮演了重要且必需的角色,为焦虑症的治疗提供了可能的研究策略和潜在的药物靶点。
[Abstract]:Anxiety disorder is one of the most prevalent mental disorders. The functional defects of 纬-aminobutyric acid, serotonin and glutaminergic system in the prefrontal cortex and amygdala are thought to be related to the pathogenesis of anxiety disorder. However, the pathological changes in cellular networks and synapses and the mechanisms involved in these regions are unclear. It has long been argued that synaptic deficits in serotonin and 纬-aminobutyric acid are associated with anxiety disorders. Selective serotonin reuptake inhibitors and 纬-aminobutyric acid receptor enhancers are used as antianxiety drugs. But because of the many side effects, the efficacy of these drugs needs to be reassessed. Recent results suggest that glutaminergic systems are also associated with anxiety disorders, and ionic glutamate receptor antagonists are considered potential antianxiety drugs. In this sense, ionic glutamate receptor agonists can theoretically induce anxiety-like behavior in mice. This paper describes the role of ionic glutamate receptor agonists in the pathological changes of anxiety disorder and its related mechanism, which provides a potential target for the treatment of anxiety disorder. We found that the ionized glutamate receptor activator, kainic acid (Kainic Acid, KA), could induce anxiety like behavior in mice, and the function and structure of excitatory synapses in the excitatory neurons of the anterior marginal cortex had been changed pathologically. The use of (Chelerythrine Chloride, CHE), a selective protein kinase C antagonist, could block the changes in behavior, synaptic function and synaptic structure induced by kainic acid in hybrid mice. These studies illustrate the role of ionic glutamate receptor agonists in the pathogenesis of anxiety disorders and the pathological function and structural changes in which protein kinase C (Protein Kinase C, PKC) plays an important and necessary role. It provides possible research strategies and potential drug targets for the treatment of anxiety disorder.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R749.72
[Abstract]:Anxiety disorder is one of the most prevalent mental disorders. The functional defects of 纬-aminobutyric acid, serotonin and glutaminergic system in the prefrontal cortex and amygdala are thought to be related to the pathogenesis of anxiety disorder. However, the pathological changes in cellular networks and synapses and the mechanisms involved in these regions are unclear. It has long been argued that synaptic deficits in serotonin and 纬-aminobutyric acid are associated with anxiety disorders. Selective serotonin reuptake inhibitors and 纬-aminobutyric acid receptor enhancers are used as antianxiety drugs. But because of the many side effects, the efficacy of these drugs needs to be reassessed. Recent results suggest that glutaminergic systems are also associated with anxiety disorders, and ionic glutamate receptor antagonists are considered potential antianxiety drugs. In this sense, ionic glutamate receptor agonists can theoretically induce anxiety-like behavior in mice. This paper describes the role of ionic glutamate receptor agonists in the pathological changes of anxiety disorder and its related mechanism, which provides a potential target for the treatment of anxiety disorder. We found that the ionized glutamate receptor activator, kainic acid (Kainic Acid, KA), could induce anxiety like behavior in mice, and the function and structure of excitatory synapses in the excitatory neurons of the anterior marginal cortex had been changed pathologically. The use of (Chelerythrine Chloride, CHE), a selective protein kinase C antagonist, could block the changes in behavior, synaptic function and synaptic structure induced by kainic acid in hybrid mice. These studies illustrate the role of ionic glutamate receptor agonists in the pathogenesis of anxiety disorders and the pathological function and structural changes in which protein kinase C (Protein Kinase C, PKC) plays an important and necessary role. It provides possible research strategies and potential drug targets for the treatment of anxiety disorder.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R749.72
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