Role of the hippocampal GABA system in the development of post-traumatic stress

海马 GABA 系统在创伤后应激发展中的作用

• 批准号: 92690057
• 负责人: Professor Dr. Uwe Heinemann (†)
• 金额: --
• 依托单位: Sagol Department of Neurobiology
• 依托单位国家: 德国
• 项目类别: DIP Programme
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/92690057?language=en
• 关键词: Role; hippocampal; GABA; system; development

Both genetic disposition and child maltreatment and abuse have been identified as majordeterminants in the development of posttraumatic stress disorder and major depression.We have recently developed a novel animal model of anxiety and affective disorders, in which theexposure of juvenile rats to stress induces a predisposition for the development of anxiety ordepressive symptoms following an emotional trauma in adulthood. We propose to use this modelsystem to explore the role of inhibitory GABAergic neurons in emotional stress in adulthood and inthe predisposition to the development of post-traumatic stress and post-traumatic depression.We focus on GABAergic mechanisms as previous work by one of us (OS) has shown that adeficiency in the GABA synthesizing enzyme, GAD65 results in increased fear and anxiety. Inaddition, we have recently shown that fear conditioning or juvenile stress can reduce the expressionof GAD65 in the amygdala. We have formed a team of four research groups with expertise ranging from behavioral analysis, to system analysis, to the molecular level with the aim of:1. Characterizing changes in postsynaptic GABAergic function in the hippocampusfollowing juvenile stress.2. Characterizing changes in properties of defined GABAergic neurons involved ingeneration of rhythmic activities and plasticity in different fields of the hippocampusfollowing stress.3. Developing strategies for intervention in the emergence of stress/depressionThe proposed project puts forward a novel, integrative approach for translational researchaddressing one of the most urgent issues in biological psychiatry today - improving treatment ofstress-related disorders, and in particular of post-traumatic stress disorder. The uniquely integratedteam assembled here ensures original and yet effective progression of the project that will yield avital understanding of the neurobiology of PTSD that is clearly lacking today.

遗传倾向和虐待儿童都被认为是创伤后应激障碍和重性抑郁症的主要决定因素。我们最近开发了一种新的焦虑和情感障碍动物模型，在该模型中，幼年大鼠暴露于压力诱导了在成年后情感创伤后发展焦虑或抑郁症状的倾向。我们建议使用这个模型系统来探索抑制性GABA能神经元在成年期情绪应激中的作用以及在创伤后应激和创伤后抑郁的易感性中的作用。我们关注GABA能机制，因为我们之一（OS）先前的工作已经表明，GABA合成酶GAD 65的缺乏会导致恐惧和焦虑的增加。此外，我们最近的研究表明，恐惧条件反射或青少年应激可以减少杏仁核中GAD 65的表达。我们已经形成了一个由四个研究小组组成的团队，其专业知识范围从行为分析到系统分析，再到分子水平，目的是：1。描述幼年应激后海马突触后GABA能功能的变化.表征应激后海马不同区域GABA能神经元的特性变化，包括节律性活动的产生和可塑性.发展战略干预出现的压力/抑郁拟议的项目提出了一种新的，综合的方法转化研究解决当今生物精神病学最紧迫的问题之一-改善治疗的压力相关的障碍，特别是创伤后应激障碍。这里组建的独特综合团队确保了该项目的原创性且有效的进展，这将使人们对创伤后应激障碍的神经生物学有深入的了解，而这在今天显然是缺乏的。