NEURAL MECHANISMS OF APNEA

新生儿的正常呼吸控制与成人一样， 在神经递质介导的网络之间的相互作用， 神经元组成脑干呼吸中枢。 然而，在这方面， 新生儿特别容易出现不稳定的呼吸道疾病， 模式，这表明在这些方面与成年人的重要差异 产后期间的互动。 长期目标是 这个实验室是为了表征兴奋性和抑制性中枢神经系统， 控制自主神经功能的神经元机制， 包括呼吸驱动。 主要 本研究的目的是描述慢性 产前缺氧作为一种长效致畸剂影响抑制性胎儿生长 递质代谢、释放和受体。 阿片类递质， 包括β-内啡肽和脑啡肽 抑制呼吸驱动，特别是对急性和 严重缺氧和其他压力。 目前的研究将是 在发育中的大鼠中进行，包括：1）鉴定正常的 发展调节机制，影响可获得性 这类用于分泌的递质。 我们将专注于 糖基化作为一种新认识的调节机制 通过翻译后调节肽的生物利用度 前体肽的加工。 2)确定影响 产前低氧血症对阿片前体基因表达的影响 翻译后阿黑皮素原和前脑啡肽原 加工这些前体多肽， 增加生物活性β-内啡肽和脑啡肽水平。 （3） 描述产前母体低氧血症对长时间妊娠的影响 新生仔鼠脑干阿片受体的长期调节 特别是在化学感受通路的神经元中。 通过定义的发展阶段的定期进展是至关重要的 呼吸控制系统的正常发育。 由于一种不正常的 围产期的状况（如缺氧）可导致 可能导致危及生命的长期系统功能障碍 病理学包括早产儿呼吸暂停、婴儿呼吸暂停 常见于较大的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.