REGULATION OF NEURONAL PHENOTYPE DURING DEVELOPMENT

在出生后早期发育过程中，化学表型(即 神经递质、肽、受体和离子通道)。 参与呼吸调节和启动呼吸的脑区 从呼吸暂停中恢复过来经历了相当大的变化。对这些的破坏 异常环境条件导致的发育模式 (如缺氧)在妊娠或出生后早期可能导致 神经元功能障碍及其危及生命的机制 对婴儿猝死综合症负有责任。上呼吸道通畅率为 对小岛屿发展中国家正常呼吸和特异性病理标志物的影响 提示上呼吸道阻塞是小岛屿发展中国家患者的常见死亡方式 这表明，一种显示上呼吸道扰动的动物模型 这一进展将为小岛屿发展中国家的病理生理学提供新的见解。 细胞组织特异性调控的分子机制 发育过程中的表型尚不清楚。一个很好的学习模型是 生长抑素及其mRNA在舌下神经中的消失 第一个月大鼠的核(NXII)。乙酰胆碱和 降钙素基因相关肽(CGRP)存在于nXII运动神经元 在整个发展过程中。我们假设SOM和CGRP基因表达 在nxII中，运动神经元调节乙酰胆碱受体成熟。 颧舌肌。第一项研究的具体目的是：1) 确定出生前和出生后缺氧影响的分子因素 NXII运动神经元SOM时间和组织特异性转录的变化 和CGRP在出生后发育早期。2)识别顺式元件 和反式作用蛋白因子，赋予发育调节 常氧和低氧条件下舌下神经元中SOM基因的表达 缺氧。以及，3)确定SOM在调节植物生长发育中的营养作用 颧舌肌组织中乙酰胆碱受体亚单位基因的表达 在常氧和低氧条件下发育。 我们的初步数据还表明，妊娠和出生后的缺氧 直接影响nxII运动神经元的电生理兴奋性 他们自己。我们假设这种机制是由于 离子通道存在于这些神经元的细胞膜上。具体的 第二项研究的目的是：1)测定生物物理膜 NXII运动神经元在不同出生年龄及以下的特性 预氧化常氧或低氧的条件以及，2)确定 预适应条件下饲养对膜离子途径的影响 和出生后缺氧。

During early postnatal development the chemical phenotype (i.e. neurotransmitter, peptide, receptors and ionic channels) of neurons in brain areas involved in regulation of respiration and initiation of and recovery from apnea undergoes considerable change. Disruption of these developmental patterns as a result of an abnormal environmental condition (eg hypoxia) during gestation or early postnatal life might lead to neuronal dysfunction and consequently life threatening mechanisms responsible for the Sudden Infant Death Syndrome. Upper airway patency is essential for normal respiration and specific pathologic markers of SIDS indicate upper airway obstruction as a common mode of death in SIDS victims suggesting that an animal model demonstrating perturbations of upper airway development will provide new insights into the pathophysiology of SIDS. Molecular mechanisms that mediate tissue-specific regulation of cell phenotype during development are unknown. An excellent model for study is the disappearance of somatostatin (SOM) and its mRNA in the hypoglossal nucleus (nXII) during the first month in the rat. Acetylcholine and calcitonin gene-related peptide (CGRP) are present in nXII motoneurons throughout development. We hypothesize that SOM and CGRP gene expression in nXII motoneurons modulate acetylcholine receptor maturation in the genioglossus muscle. The Specific Aims of this first study are: 1) To determine molecular factors affected by pre- and postnatal hypoxia that change temporal- and tissue-specific transcription of nXII motoneuron SOM and CGRP during early postnatal development. 2) To identify cis-elements and trans-acting protein factors that confer developmental regulation of the SOM gene in the hypoglossal neurons under conditions of normoxia and hypoxia. And, 3) to determine the trophic role of SOM in regulation of acetylcholine receptor subunit gene expression in genioglossus muscle during development in normoxia and hypoxia. Our preliminary data also indicate that gestational and postnatal hypoxia directly affects electrophysiologic excitability of nXII motoneurons themselves. We hypothesize that this mechanism is due to alterations in the ionic channels present in the membranes of these neurons. The Specific Aims of the second study are: 1) To determine biophysical membrane properties of nXII motoneurons at different postnatal ages and under conditions of prexisiting normoxia or hypoxia. And, 2) to determine which membrane ionic pathways are affected by rearing under conditions of pre- and postnatal hypoxia.