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的脑区， 从呼吸暂停的恢复经历了相当大的变化。破坏这些 异常环境条件导致的发育模式 (eg缺氧）可能导致 神经元功能障碍和因此威胁生命的机制 婴儿猝死综合症的罪魁祸首 上呼吸道通畅 对于正常呼吸和SIDS的特定病理标志物至关重要 表明上呼吸道阻塞是SIDS患者常见死亡方式 表明显示上呼吸道扰动的动物模型 发展研究将为小岛屿发展中国家的病理生理学提供新的见解。 介导细胞组织特异性调节的分子机制 在发育过程中的表型是未知的。 一个很好的学习模式是 舌下神经生长抑素（SOM）及其mRNA的消失 核（nXII）在第一个月的大鼠。 乙酰胆碱和 降钙素基因相关肽（CGRP）存在于nXII运动神经元中 在整个发展中。 我们假设SOM和CGRP基因表达 在nXII运动神经元调节乙酰胆碱受体的成熟， 颏舌肌 第一项研究的具体目的是：1） 确定受产前和产后缺氧影响的分子因素， 改变nXII运动神经元SOM的时间和组织特异性转录 和CGRP在出生后早期发育中的作用。2)鉴定顺式元件 和反式作用蛋白质因子， 在常氧条件下舌下神经元的SOM基因， 缺氧 3）确定SOM在调节植物生长中的营养作用。 颏舌肌乙酰胆碱受体亚单位基因表达 在常氧和缺氧条件下发育。 我们的初步数据还表明， 直接影响nXII运动神经元的电生理兴奋性 自己 我们假设，这种机制是由于改变， 存在于这些神经元的膜中的离子通道。 具体 第二项研究的目的是：1）确定生物物理膜 不同生后年龄及以下nXII运动神经元的特性 预存常氧或缺氧的条件。 （2）确定哪些 膜离子途径受饲养条件下的预- 和产后缺氧

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.