果蝇中枢神经调节气管感知氧的机制研究

脑是人体高耗氧器官。新生儿易发的缺氧缺血性脑病（HIE），可造成新生儿永久性神经功能障碍。临床研究显示，宫内缺氧缺血与儿童期自闭症谱系障碍（ASD）强相关；有些ASD患儿还表现出呼吸障碍。有研究发现，自闭症相关基因产物NRX缺失的小鼠自出生起普遍出现呼吸困难，但机制不明。我们在应用模式生物果蝇研究DNRX基因功能的过程中，意外地发现DNRX缺失的果蝇会引起呼吸障碍和脑缺氧现象。由此提出新假说：NRX表达于果蝇气管相关的神经元中，介导机体对氧的感知，调节氧的利用。本项目将研究：1）果蝇DNRX影响神经中枢气管结构和功能的分子机制；2）果蝇神经中DNRX调节机体感知和摄取氧气的方式。以期解析神经突触粘附分子DNRX介导神经系统和呼吸系统互作的分子机制，为探究机体内部感受器的工作原理与自稳态调节、自闭症的致病机理以及指导临床治疗与干预奠定基础。

The brain is a high oxygen consuming organ of the human body. Newborns prone of hypoxic ischemic encephalopathy (HIE), which can cause neonatal permanent nerve dysfunction. Clinical study showed that intrauterine hypoxia ischemia and childhood autism spectrum disorders (ASD) strong correlation; Some children with ASD showed respiratory disorder. Consistently, autism-related gene, neurexin knock-out mice show dyspnea from birth in common as well, however, the mechanism is unknown. Furthermore, we found accidentally DNRX mutant flies showed hypoxia and breathing problems in Drosophila larvae, when we investigated neurodevelopment using the model organism Drosophila. Based on those findings, a new hypothesis is proposed: NRX may express in tracheal dendrite neurons in fruit flies, and mediates oxygen sensors in tracheal system of Drosophila, that regulates the use of oxygen. This project will study: 1) to elucidate the molecular mechanism of tracheal structure formation and function in central nerve system by DNRX; 2) to illuminate the regulation of perceiving and intake of oxygen by DNRX in the Drosophila. Hoping more insight into molecular mechanism of interaction of the nervous system and respiratory system mediated by the synaptic DNRX adhesion molecules, further to explore the body's internal principle of sensor and homeostasis, the pathogenesis of autism and lay a foundation to guide the clinical treatment and intervention.