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Targeting astroglial metabolism in vivo: Consequences for astrocytes, neurons and synapses

体内靶向星形胶质细胞代谢：对星形胶质细胞、神经元和突触的影响

基本信息

批准号：
82286537
负责人：
Professor Dr. Johannes Hirrlinger, Ph.D.
金额：
--
依托单位：
Carl-Ludwig-Institut für Physiologie
依托单位国家：
德国
项目类别：
Priority Programmes
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2010-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/82286537?language=en
关键词：
Targeting astroglial metabolism vivo Consequences

项目摘要

Metabolic cooperation between different types of brain cells is necessary for proper brain function like synaptic transmission and plasticity. The NAD+ / NADH-redox state is a central point of cellular metabolism, and is coupled to neuronal activity as well as to the metabolic interaction of astrocytes and neurons. It also regulates gene expression, protein functions and signalling properties of cells. However, it has been difficult to appreciate cell type specific metabolic contributions to brain functions in situ and in vivo due to the enormous complexity of cell types and the lack of cell type specific intervening strategies. In this project, we aim to analyse the impact of a shifted astroglial NAD+ / NADH-redox state on astrocytes and neighbouring neurons regarding gene expression, astroglial and synaptic signalling, and structural plasticity. This will be achieved by taking advantage of a transgenic mouse model based on a new strategy, that allows to precisely shift the NAD+ / NADH-redox state in an inducible and, importantly, a cell type-specific manner in vivo. These experiments will provide novel insights how (astroglial) metabolism contributes to synaptic function and plasticity by integrating metabolic states, gene expression and signalling.

不同类型的脑细胞之间的代谢合作对于正常的大脑功能，如突触传递和可塑性是必要的。NAD+/NADH-氧化还原状态是细胞代谢的中心点，与神经元的活动以及星形胶质细胞和神经元的代谢相互作用有关。它还调节细胞的基因表达、蛋白质功能和信号特性。然而，由于细胞类型的巨大复杂性和缺乏细胞类型特异性干预策略，在原位和体内很难评价细胞类型特异性代谢对脑功能的贡献。在这个项目中，我们旨在分析星形胶质细胞NAD+/NADH-氧化还原状态的改变对星形胶质细胞和邻近神经元在基因表达、星形胶质细胞和突触信号以及结构可塑性方面的影响。这将通过利用基于新策略的转基因小鼠模型来实现，该新策略允许在体内以可诱导的、更重要的是细胞类型特异性的方式精确地改变NAD+/NADH-氧化还原状态。这些实验将提供新的见解，(星形胶质)代谢如何通过整合代谢状态、基因表达和信号来促进突触功能和可塑性。