Postnatal Intermittent Hypoxia and Respiration: Potenti*

描述（由申请人提供）：间歇性缺氧（IH）是临床医学中常见的疾病（如睡眠呼吸暂停，SIDS），具有很高的发病率和死亡率。此外，对IH的有机体适应表明形成了特定形式的神经元可塑性。虽然已经在成熟哺乳动物中进行了大量关于IH影响的研究，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，几乎没有任何研究。因此，我们假设出生后间歇性缺氧，如睡眠呼吸暂停，可能会导致呼吸控制的长期改变，从而导致呼吸模式的一种元可塑性。由产后早期IH引起的呼吸网络的后一种改变可能对呼吸反应系统造成功能上的有利或不适应的改变。为了研究这个问题，我们将：(i)描述出生后IH对自由行为大鼠的常氧通气和低氧和高碳酸血症通气反应的影响；（ii）评估IH对膈运动神经长期促进（LTF）的影响；（iii）确定信号通路的潜在作用，特别是蛋白激酶C (PKC)，在IH通过发育造成的通气的长期改变中。因此，这项工作将有助于理解介导IH早期适应的潜在机制，同时也为在关键成熟阶段施加条件刺激时可能发生的通气长期变化提供见解。

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.