REGULATION OF PEPTIDE EXPRESSION IN NEURONAL CELL

描述：这是第二个修改后的应用程序 上级神经递质/神经肽表达的一般问题 颈神经节细胞。基于之前的批评和 其他初步调查结果，申请人现在建议使用 培养SCG神经元以检验顺行信号的假说 (以PACAP(垂体腺苷环化酶激活)为代表 多肽)和逆行信号(以CDF/LIF为代表 (胆碱能分化因子/白血病抑制因子) 差异调节细胞的合成、含量、信使核糖核酸和释放 特异性交感神经递质和神经肽通过 受体介导的特异性细胞内信号的激活 小路。生化、分子和形态方法将是 用来进一步达到2个特定目的：1)研究PACAP的发病机制 突触前调节SCG神经元NPY和儿茶酚胺的表达， 2)研究CDF/LIF对SCG神经递质的调节作用 神经肽表达与神经表型可塑性。对于每一个 这些目标，将解决4个基本问题：1)是否有 NPY和儿茶酚胺的不同调节？2)什么是 表达改变的细胞基础是什么？3)有哪些受体 调节这些活动？4)什么是细胞内信号 受这些因素调控的机制？ 这些研究将开始描绘引导细胞事件 神经递质和肽在发育、应激、 损伤和再生。

DESCRIPTION: This is the second revised application addressing the general question of neurotransmitter/neuropeptide expression in superior cervical ganglion cells. Based both on previous criticism and on additional preliminary findings, the applicant now proposes to use cultured SCG neurons to examine the hypothesis that anterograde signals (represented by PACAP (pituitary adenylate cyclase activating polypeptide) peptides) and retrograde signals (represented by CDF/LIF (cholinergic differentiation factor/leukemia inhibitory factor)) differentially regulate the biosynthesis, content, mRNA and release of specific sympathetic neuron transmitters and neuropeptides through receptor-mediated activation of specific intracellular signaling pathways. Biochemical, molecular and morphological approaches will be used to further 2 specific aims: 1) To examine the mechanism of PACAP presynaptic regulation of SCG neuronal NPY and catecholamine expression, and 2) To investigate CDF/LIF regulation of SCG neurotransmitter and neuropeptide expression and neurophenotypic plasticity. For each of these aims, 4 basic questions will be addressed: 1) Is there differential regulation specific for NPY and catecholamines? 2) What is the cellular basis for the altered expression? 3) What receptors are mediating the actions? 4) What are the intracellular signaling mechanisms regulated by these factors? These studies will begin to delineate the cellular events that guide neuronal transmitter and peptide expression in development, stress, injury and regeneration.