Ciliary Neurotrophic Factor and Synaptic Components in Developing Chick Heart

发育中的鸡心脏中的睫状神经营养因子和突触成分

• 批准号: 9728881
• 负责人: Stanley Halvorsen
• 金额: $ 6.3万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9728881&HistoricalAwards=false
• 关键词: Ciliary; Neurotrophic; Factor; Synaptic; Components

9728881 HALVORSEN The secreted, biologically active molecules called cytokines play key roles in the differentiation and maturation of a variety of tissues during embryonic development. It is important to determine the molecular mechanisms for these cytokine actions for a general understanding of nervous system development. The recently described "neuropoietic" cytokines have potential roles in the developing nervous and cardiovascular systems which are, as yet, largely undefined. The overall goal of this study is to understand the functional role of the cytokine ciliary neurotrophic factor (CNTF) in development of the heart and its innervation. The mechanisms important for expression of CNTF receptors during development will be investigated, the molecular mechanisms that regulate these receptors in heart tissue and in cultured myocytes during parasympathetic synapse formation will be defined, and the effects of CNTF on key synaptic components will be identified in the heart. Upon completion of the project three fundamental questions will have been addressed. (1) Does the change in CNTF receptor levels result in changes in tissue CNTF sensitivity? (2) What is (are) the mechanism(s) of regulation of CNTF receptors in heart? (3) Does CNTF play a role in parasympathetic synapse formation in the developing atria? Over the long term, downstream gene and biochemical targets of CNTF and related cytokine action in heart will be determined. These studies represent some of the first to define the expression and function of CNTF receptors in the cardiovascular system. With this new information we will have a better understanding of the mechanisms that regulate nerve-heart cell responses to cytokines during embryonic development and of mechanisms that may be important for maintenance of these functions in the adult.

小行星9728881 被称为细胞因子的分泌的生物活性分子在胚胎发育期间的各种组织的分化和成熟中起关键作用。 确定这些细胞因子作用的分子机制对于神经系统发育的一般理解是重要的。 最近描述的“神经生成”细胞因子在发育中的神经和心血管系统中具有潜在的作用，但这些作用在很大程度上尚未确定。本研究的总体目标是了解细胞因子睫状神经营养因子（CNTF）在心脏发育及其神经支配中的功能作用。CNTF受体在发育过程中表达的重要机制将被研究，在副交感神经突触形成过程中调节心脏组织和培养的肌细胞中这些受体的分子机制将被定义，CNTF对心脏关键突触成分的影响将被确定。 项目完成后，将解决三个基本问题。(1)CNTF受体水平的变化是否导致组织CNTF敏感性的变化？ (2)心脏中CNTF受体的调节机制是什么？ (3)CNTF在发育中的心房副交感神经突触形成中发挥作用吗？ 从长远来看，CNTF的下游基因和生化靶点以及相关细胞因子在心脏中的作用将被确定。这些研究代表了第一批确定CNTF受体在心血管系统中的表达和功能的研究。有了这些新的信息，我们将有一个更好的了解机制，在胚胎发育过程中调节神经心脏细胞对细胞因子的反应和机制，可能是重要的维持这些功能在成人。