Neurocognitive Consequences of Intermittent Hypoxia

项目摘要 睡眠呼吸暂停是一种呼吸系统疾病，在整个睡眠周期中引起慢性间歇性缺氧。 神经影像学研究表明，海马体特别容易受到睡眠呼吸暂停的伤害。在 除了这种大脑结构与空间和识别记忆有关外， 与外周化学反射和呼吸模式偶联并对其施加影响。因此，沿着 认知效应，海马的神经生理学变化可能有助于 心血管疾病，中风的风险增加，发生未经治疗的睡眠呼吸暂停。的持续时间 未经治疗的睡眠呼吸暂停持续存在，病情的严重程度增加， 越来越严重的认知缺陷。我们假设睡眠引起的慢性间歇性缺氧 呼吸暂停触发活性氧信号，导致海马神经元持续时间依赖性变化。 神经生理学，并进而导致基于大脑的认知的进行性退化。我们测试这个 在啮齿动物睡眠呼吸暂停模型中，动物暴露于不同持续时间的慢性呼吸暂停， 间歇性缺氧我们研究了对海马神经生理学和神经发生的影响， 重点研究参与学习和记忆途径的主要神经元。除了剖析 在认知变化中的活性氧信号，我们探讨了这种信号的机制起源， 心肺器官之间的潜在相互作用（即，颈动脉体）和海马体。的 从这项工作中获得的机械见解将为开发更有效的治疗方法提供信息， 或完全逆转认知能力下降的状况，这种状况影响了许多美国人的生活质量。

PROJECT SUMMARY Sleep apnea is a respiratory disorder that causes chronic intermittent hypoxia throughout the sleep cycle. Neuroimaging studies indicate that the hippocampus is particularly vulnerable to injury in sleep apnea. In addition to the involvement of this brain structure with spatial and recognition memory, hippocampal activity is coupled to and exerts influence on peripheral chemoreflexes and respiratory patterns. Thus, along with its cognitive effects, the neurophysiological changes in the hippocampus may contribute to the development of cardiovascular disease, the increased risk for stroke that occur with untreated sleep apnea. As the duration of untreated sleep apnea persists, the severity of the condition increases, as does the risk of developing increasingly significant cognitive deficit. We hypothesize that chronic intermittent hypoxia caused by sleep apnea triggers reactive oxygen species signaling, resulting in duration-dependent changes to hippocampal neurophysiology and, in turn, causing progressive degradation in hippocampal-based cognition. We test this hypothesis in a rodent model of sleep apnea in which animals are exposed to different durations of chronic intermittent hypoxia. We examine the resulting effects on hippocampal neurophysiology and neurogenesis, focusing on principal neurons involved in learning and memory pathways. In addition to dissecting the role of reactive oxygen species signaling in cognitive changes, we explore the mechanistic origin of this signaling and the potential interaction between cardio-respiratory organs (i.e., carotid bodies) and the hippocampus. The mechanistic insights gained from this work will inform the development of more effective therapies to prevent, or fully reverse, cognitive decline in a condition that affects the quality of life for many Americans.