NEURAL MECHANISMS OF APNEA

新生儿的正常呼吸控制，就像成年人一样，依赖于 关于神经递质介导的网络之间的相互作用 组成脑干呼吸中枢的神经元。然而， 新生儿特别容易患上不稳定的呼吸道 模式，这表明在这些方面与成年人有重要的区别 在出生后时期的相互作用。的长远目标 本实验室将研究兴奋性和抑制性中枢 控制自主神经功能的神经机制， 包括呼吸驱动，在新生儿期。少校 本研究的目的是描述慢性阻塞性肺疾病的疗效 产前低氧作为一种长效致畸因子影响对小鼠的抑制作用 递质代谢、释放和受体。阿片类递质， 包括β-内啡肽和脑啡肽，与 对呼吸动力的抑制，尤其是在应对急性和 严重的缺氧和其他压力。目前的研究将是 在发育中的大鼠身上执行，包括：1)识别正常 影响可获得性的发育调节机制 这类分泌物的传递器。我们将重点关注 糖基化--一种新的调控机制 翻译后调节多肽的生物利用度 前体多肽的加工(S)。2)确定 产前低氧血症对阿片前体基因表达的影响 原阿片黑素皮质素和前脑啡肽原，翻译后 加工这些前体多肽，并产生瞬时的 增加生物活性的β-内啡肽和脑啡肽水平。和，3) 围产期母体低氧血症对围产儿的影响 新生仔鼠脑干阿片受体的时程调节 尤其是在化学感觉通路的神经元中。 在确定的发育阶段中有规律地发展是至关重要的 呼吸控制系统的正常发育。 由异常引起的正常发育模式的中断 围产期的状况(如缺氧)可导致 长期的系统功能障碍可能导致生命危险 病理包括早产儿呼吸暂停、婴儿呼吸暂停 常见于大龄婴儿和婴儿猝死综合症。

Normal respiratory control in newborns, as in adults, is dependent upon neurotransmitter mediated interactions among networks of neurons comprising the brainstem respiratory centers. However, newborns are particularly prone to develop unstable respiratory patterns, suggesting important differences from adults in these interactions during the postnatal period. The long-range goal of this laboratory is to characterize excitatory and inhibitory central neuronal mechanisms which control autonomic nervous function, including respiratory drive, during the newborn period. The major objective of the present study is to characterize the effect of chronic prenatal hypoxia as a long-acting teratogen affecting inhibitory for transmitter metabolism, release and receptors. Opioid transmitters, including beta-endorphin and enkephalin, are associated with inhibition of respiratory drive, particularly in response to acute and severe hypoxia and other stresses. The present studies are to be performed in developing rats and include: 1) Identifying normal developmentally regulated mechanisms which affect availability of this class of transmitter for secretion. We will focus on glycosylation as a newly recognized mechanism regulating bioavailability of the peptides through regulation of post-translation processing of precursor peptide(s). 2) Determining the effect of prenatal hypoxemia on gene expression of the opioid precursors proopiomelanocortin and preproenkephalin, post-translation processing these precursor polypeptides, and creation of transiently increased bioactive beta-endorphin and enkephalin levels. And, 3) Characterizing the effects of prenatal maternal hypoxemia on long term regulation of opioid receptors in the newborn pup brainstem and specifically in neurons of the chemosensory pathway. Regular progression through defined developmental stages is crucial for normal development of the respiratory control system. Disruption of the normal developmental pattern due to an abnormal condition (e.g. hypoxia) during the perinatal period can lead to protracted system dysfunction possibly resulting in life threatening pathologies including apnea in premature infants, infantile apnea common in older infants, and Sudden Infant Death Syndrome.