高盐摄入对果蝇睡眠行为的影响规律及分子神经机制研究

长期高盐摄入不仅与人类多种慢性疾病的发生有直接的关系，而且对大脑神经系统和认知功能造成危害。作为高级神经系统相关的生理行为，睡眠一直是神经生理学研究的热点。其中，果蝇是睡眠研究的理想模式，我们前期研究发现高盐摄入导致年轻果蝇提早表现出类似年老个体的表型，即运动异常并出现片段化睡眠，但其背后涉及的分子机制及相关神经回路尚不清楚。本项目拟采用系统生物学和遗传学手段对此开展深入探讨。重点研究果蝇高盐摄入后其消化系统和大脑在代谢组和转录组水平发生的变化，利用基因集富集分析和多组学关联分析找出关键信号通路及基因。然后利用经典的果蝇遗传学手段对相关基因及信号通路进行验证，利用先进的光遗传学操作手段对神经回路进行验证，最终建立高盐摄入调控睡眠和活动行为的核心分子及神经机制。该项目的实施对于理解高盐摄入如何影响睡眠生理具有重要的意义。同时，为指导人们健康饮食和减盐等公共决策提供科学依据。

Long-term high-salt intake is not only directly related to the occurrence of many chronic diseases in humans, but also impairs the nervous system and cognitive function. As an advanced neurological-related physiological behavior, sleep remains a broadly interesting for neurophysiological researches. Among them, Drosophila is an ideal model. In our previous study, we found that high-salt intake caused young Drosophila to exhibit a phenotype similar to that of an elderly individual, that is, abnormal activity and fragmented sleep. However, we still know very little about the molecular mechanisms and related neural circuits. Here, this proposal intends to reveal them using systems biology and genetic methods. Firstly, we focus on the changes in the digestive system and brain at the metabolome and transcriptome levels after high-salt intake. And then the gene set enrichment analysis and the multi-omics association analysis are used to identify the key signaling pathways and genes. Secondly, the classical Drosophila genetic method is employed to verify the related genes and signal pathways. Finally, the advanced optogenetic method is conducted to verify the neural circuits. Overall, the core molecules and the neural mechanisms for high-salt intake-mediated regulation of sleep and activity behavior will be established in this project. The implementation of this project will help us to understand how high-salt intake affects the physiological of sleep. At the same time, it will provide a scientific basis for guiding people in healthy eating, or for public decision-making such as salt reduction.