The influence of disease-associated mutations on dendritic and synapse structure

疾病相关突变对树突和突触结构的影响

• 批准号: 215553798
• 负责人: Dr. Britta Schürmann
• 金额: --
• 依托单位: Department of Physiology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/215553798?language=en
• 关键词: influence; disease; associated; mutations; dendritic

Neuropsychiatric disorders such as autism spectrum disorder, schizophrenia or Alzheimer’s disease have a high prevalence and a strong genetic component. To improve treatment strategies it is important to understand the complex interplay of the underlying genetic architecture, cellular substrates and brain circuits that define specific disease profiles. Much evidence indicates that the signaling pathways that control the communication between neurons by altering the size and the shape of their main communication sites, called synapses, are dysregulated in the disease context. Interestingly, many of the risk genes identified in neuropsychiatric disorders encode proteins that are implicated in neuronal communication. Within the scope of the proposed research, I will focus on one of these proteins, that is thought to participate in these signaling pathways. Furthermore, alterations in its amino acid sequence have been identified in patients’ families and not in healthy controls. However, the impact of these mutations on neuronal structure and function in the intact brain is not known. I will use state-of-the-art genetic and imaging tools to express the disease-associated variants and to analyze their impact on neuron and synapse structure. This project will link a disease-associated molecule with structural alterations in the intact brain and in addition to its relevance for disease it will also analyze key mechanisms underlying basic brain development and connectivity.

神经精神障碍，如自闭症谱系障碍、精神分裂症或阿尔茨海默氏病的患病率很高，遗传因素很强。为了改善治疗策略，重要的是要了解潜在的遗传结构，细胞基质和大脑回路的复杂相互作用，定义特定的疾病概况。许多证据表明，通过改变其主要通信部位（称为突触）的大小和形状来控制神经元之间通信的信号通路在疾病背景下失调。有趣的是，在神经精神疾病中发现的许多风险基因编码与神经元通讯有关的蛋白质。在拟议的研究范围内，我将专注于这些蛋白质之一，这被认为是参与这些信号通路。此外，其氨基酸序列的改变已在患者的家庭中被确定，而不是在健康对照中。然而，这些突变对完整大脑中神经元结构和功能的影响尚不清楚。我将使用最先进的遗传和成像工具来表达疾病相关的变异，并分析它们对神经元和突触结构的影响。该项目将把疾病相关分子与完整大脑中的结构改变联系起来，除了与疾病的相关性外，还将分析基本大脑发育和连接的关键机制。