Postnatal Intermittent Hypoxia and Respiration: Potenti*

描述(申请人提供)：间歇性低氧(IH)是临床医学中常见的疾病(如睡眠呼吸暂停，SID)，具有相当高的发病率和死亡率。此外，机体对IH的适应暗示了特定形式的神经元可塑性的形成。虽然在成熟哺乳动物中已经对IH的影响进行了大量的研究，但在出生后发育的早期阶段，即神经元脆弱和适应的独特时期，几乎没有做过任何工作。因此，我们假设，出生后间歇性低氧，如睡眠呼吸暂停，可能会对呼吸控制施加长期的修改，从而导致某种形式的呼吸模式的可塑性。由出生后早期IH引起的呼吸网络的后一种改变可能会对呼吸反应系统造成功能上的有利或不适应的改变。为了研究这一问题，我们将：(I)表征生后IH对正常行为大鼠呼吸的影响，以及对自由行为大鼠低氧和高二氧化碳呼吸反应的影响。(Ii)评估IH对膈运动神经长期易化(LTF)的影响。(Iii)确定信号通路，特别是蛋白激酶C(PKC)，在IH通过发育施加的长期呼吸机能调节中的潜在作用。因此，这项工作将有助于理解不仅介导对IH的早期适应的潜在机制，而且还将为在成熟的关键阶段应用条件性刺激时可能发生的长期换气变化提供见解。

DESCRIPTION (provided by applicant): Intermittent hypoxia (IH) is a frequent condition in clinical medicine (e.g., sleep apnea, SIDS), which bears substantial morbidity and mortality. Furthermore, organismal adaptations to IH suggest the formation of specific forms of neuronal plasticity. While substantial study of the effects of IH has been performed in the mature mammal, little if any work has been done during the early phases of post-natal development, a unique period of neuronal vulnerability and adaptation. Therefore, we hypothesized that post-natal intermittent hypoxia, such as occurs in sleep apnea, may impose long-term modifications in respiratory control, thereby leading to a form of metaplasticity of respiratory patterning. The latter modification of the respiratory network induced by early post-natal IH could impose either a functionally favorable or a maladaptive alteration of the respiratory response system. To examine this issue, we will: (i) characterize the effects of post-natal IH on normoxic ventilation and on hypoxic and hypercapnic ventilatory responses in freely behaving rats.; (ii) assess the effects of IH on phrenic motor nerve long-term facilitation (LTF).; (iii) determine the potential role of signaling pathways, particularly protein kinase C (PKC), in the long-term modification of ventilation imposed by IH through development. This work will therefore contribute to the understanding of potential mechanisms mediating not only early adaptations to IH but also provide insights to long-lasting changes in ventilation that may develop when a conditioning stimulus is applied during critical phase of maturation.