Plasticity in the central neural control of the upper airway

上呼吸道中枢神经控制的可塑性

• 批准号: 116653729
• 负责人: Dr. Georg Martin Stettner
• 金额: --
• 依托单位: Mahoney Institute of Neurosciences
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/116653729?language=en
• 关键词: Plasticity; central; neural; control; upper

Obstructive sleep apnea (OSA) is a common disorder that affects both children and adults. Its main manifestation is the patients’ inability to maintain the airway open during sleep leading to sleep loss and fragmentation, impaired alertness, arterial hypertension and metabolic disorders. The state-dependence of OSA points to a central role of the interaction between control of sleep-wake states and control of breathing. OSA patients are sleep-deprived and develop an adaptive increase in the activity of their upper airway muscles. Whereas the latter adaptation helps them maintain normal breathing during wakefulness, the increased drive for sleep exacerbates OSA conditions by increasing frequency and severity of sleep-related upper airway obstructions.These phenomena have been extensively described and discussed, but studies in humans are limited in their ability to elucidate the underlying cellular, neurochemical and molecular mechanisms. The goal of the planned research is to unveil the central neural mechanisms responsible for the altered control of the upper airway using rodent models. The studies will combine monitoring of upper airway muscle activity across the sleep-wake cycle in chronically instrumented rats with quantitative studies of gene and protein expression in brain regions responsible for the control of upper airways. To model the conditions similar to those in OSA patients, rodents will be subjected to manipulations such as sleep deprivation, exposures to alternating levels of oxygen and surgical interventions that increase the load on upper airway muscles.

阻塞性睡眠呼吸暂停（OSA）是一种影响儿童和成人的常见疾病。其主要表现为患者在睡眠中无法保持气道畅通，导致睡眠缺失和破碎，警觉性受损，动脉高血压和代谢紊乱。OSA的状态依赖性指出了睡眠-觉醒状态控制和呼吸控制之间相互作用的核心作用。阻塞性睡眠呼吸暂停患者睡眠不足，上呼吸道肌肉的活动出现适应性增加。尽管后一种适应有助于他们在清醒时保持正常呼吸，但睡眠驱动的增加会增加与睡眠相关的上呼吸道阻塞的频率和严重程度，从而加剧OSA病情。这些现象已经被广泛地描述和讨论过，但是对人类的研究在阐明潜在的细胞、神经化学和分子机制方面的能力有限。计划研究的目标是利用啮齿动物模型揭示负责改变上呼吸道控制的中枢神经机制。这些研究将结合对长期使用仪器的大鼠在睡眠-觉醒周期中上呼吸道肌肉活动的监测，以及对负责控制上呼吸道的大脑区域的基因和蛋白质表达的定量研究。为了模拟类似于OSA患者的情况，啮齿动物将受到诸如睡眠剥夺，暴露于交替的氧气水平和手术干预等操作，以增加上呼吸道肌肉的负荷。