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Neurocognitive Consequences of Intermittent Hypoxia

Neurocognitive Consequences of Intermittent Hypoxia
间歇性缺氧的神经认知后果
批准号:
10400110
负责人:
Alfredo J Garcia
金额:
$35.44万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-05-01 至 2024-04-30

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中文摘要
翻译
项目总结 睡眠呼吸暂停是一种呼吸系统疾病,在整个睡眠周期中会导致慢性间歇性低氧。 神经成像研究表明,在睡眠呼吸暂停症中,海马体特别容易受到损伤。在……里面 除了参与这种具有空间和识别记忆的大脑结构外,海马体的活动 结合并对外周化学反射和呼吸模式产生影响。因此,连同它的 认知效应,海马区的神经生理学变化可能有助于 心血管疾病,未经治疗的睡眠呼吸暂停症导致的中风风险增加。作为持续时间 未经治疗的睡眠呼吸暂停持续存在,病情的严重性增加,发展的风险也增加。 日益严重的认知缺陷。我们假设睡眠引起的慢性间歇性低氧 呼吸暂停触发活性氧信号,导致海马区持续时间依赖的改变 神经生理学,进而导致以海马体为基础的认知的进行性退化。我们对此进行测试 动物暴露于不同持续时间的慢性睡眠呼吸暂停的啮齿动物模型的假说 间歇性缺氧。我们研究了由此产生的对海马神经生理学和神经发生的影响, 重点关注参与学习和记忆通路的主要神经元。除了剖析其角色 在认知变化中的信号转导,我们探索这种信号的机制起源和 心肺器官(即颈动脉小体)和海马体之间的潜在相互作用。这个 从这项工作中获得的机械性见解将为开发更有效的治疗方法提供信息,以预防、 或者完全逆转,认知能力下降,这会影响许多美国人的生活质量。
英文摘要
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.
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Mechanisms of repeated opioid use dependent remodeling in respiratory control
  • 批准号:
    10539902
  • 项目类别:
  • 资助金额:
    $64.37万
  • 财政年份:
    2022
  • 负责人:
    Alfredo J Garcia
  • 依托单位:
Mechanisms of repeated opioid use dependent remodeling in respiratory control
  • 批准号:
    10677776
  • 项目类别:
  • 资助金额:
    $67.09万
  • 财政年份:
    2022
  • 负责人:
    Alfredo J Garcia
  • 依托单位:
Mechanisms of repeated opioid use dependent remodeling in respiratory control
  • 批准号:
    10713911
  • 项目类别:
  • 资助金额:
    $41.0万
  • 财政年份:
    2022
  • 负责人:
    Alfredo J Garcia
  • 依托单位:
Neurocognitive Consequences of Intermittent Hypoxia
  • 批准号:
    10302877
  • 项目类别:
  • 资助金额:
    $2.77万
  • 财政年份:
    2021
  • 负责人:
    Alfredo J Garcia
  • 依托单位:
海外基金