REGULATION OF CAROTID BODY AFFERENT DEVELOPMENT

这项拟议中的研究旨在定义细胞和分子 调节围产期颈动脉体成熟的机制 大鼠的传入神经元。 这些细胞位于 岩神经节（PG），构成之间的感觉通路， 颈动脉体化学感受器和脑干，从而发挥 在调节对这种生活的反应中起着关键作用- 威胁性刺激如缺氧。 然而，颈动脉体反射 在胎儿、新生儿和成人生命之间的变化，以及 对这一发展的基础知之甚少。 颈 化学感受器是相对无效的，例如在增加 胎儿缺氧时的呼吸反应;出生后， 缺氧刺激产生短暂的，并最终持续 呼吸增加。 我们实验室最近的研究 表明由以下物质表达儿茶酚胺能（CA）性质 围产期PG内颈动脉体传入纤维明显增加 期间，表明时间上的，可能是因果关系， 化学反射发育 因此，为了阐明围产期 调节颈动脉体传入神经的发育，建议 旨在进一步定义PG中CA的成熟， 研究潜在生理、细胞和分子 机制等 生化、免疫细胞化学和组织化学 方法将用于描述产前和产后 儿茶酚胺生物合成酶酪氨酸的开发 羟化酶（TH）和儿茶酚胺荧光。 生理 研究将探索这种可能性， 出生后产生的氧气，以及出生过程本身， 参与CA成熟的影响，通过检查慢性 缺氧和剖宫产对TH和儿茶酚胺发育影响 此外，组织培养方法将用于 研究分子机制，如营养相互作用， 去极化刺激，可能影响围产期成熟 颈动脉体传入神经元。 这些研究是 旨在确定心肺传入神经的长期努力 分子水平的发展。 希望这项工作 有助于阐明肺换气不足的分子发病机制 综合征，并导致新的治疗 接近。 这项拟议中的研究也可能揭示基本的 神经发育的机制，适用于神经 整个系统。

The proposed research seeks to define cellular and molecular mechanisms that regulate the perinatal maturation of carotid body afferent neurons in the rat. These cells, localized to the petrosal ganglion (PG), constitute the sensory pathway between the carotid body chemoreceptor and the brainstem, and thereby play a pivotal role in mediating ventilatory responses to such life- threatening stimuli as hypoxia. However, carotid body reflexes change between fetal, neonatal and adult life, and mechanisms that underlie this development are poorly understood. Carotid chemoreceptor are relatively ineffective, for example in increasing ventilatory responses during hypoxia in the fetus; after birth, hypoxic stimulation produces transient, and eventually sustained increases in respiration. Recent studies in our laboratory indicate that catecholaminergic (CA) properties expressed by carotid body afferents in the PG increase markedly in the perinatal period, indicating a temporal, and possibly causal relationship to chemoreflex development. Therefore, to elucidate the perinatal regulation of carotid body afferent development, the proposal is designed to further define CA maturation in the PG and to investigate underlying physiological, cellular and molecular mechanisms. Biochemical, immunocytochemical and histochemical methods will be used to delineate the pre- and postnatal development of the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) and catecholamine fluorescence. Physiologic studies will explore the possibility that the increase in inspired O2 that occurs after birth, as well as birth process itself, are involved in CA maturation by examining the effects of chronic hypoxia and Cesarean delivery on TH and catecholamine development in the PG. Moreover, tissue culture methods will be used to examine molecular mechanisms, such as trophic interactions and depolarizing stimuli, that may influence the perinatal maturation of carotid body afferent neurons. These studies are part of a long-range effort aimed at defining cardiopulmonary afferent development at the molecular level. It is hoped that this work will help elucidate the molecular pathogenesis of hypoventilation syndromes in infants and adults and lead to new therapeutic approaches. The proposed research may also shed light on basic mechanisms of neuronal development, applicable to the nervous system as a whole.