REGULATION OF NEURONAL GROWTH AND DEVELOPMENT

神经元生长和发育的调节

• 批准号: 3394192
• 负责人: IRA B BLACK
• 金额: $ 18.77万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3394192
• 关键词: aging; brain cell; central nervous system; complementary DNA; developmental genetics; embryo /fetus; enkephalins; enzyme mechanism; gene expression; guinea pigs; histochemistry /cytochemistry; immunochemistry; laboratory rabbit; laboratory rat; mature animal; messenger RNA; molecular genetics; neural information processing; neural plasticity; neuroanatomy; neurochemistry; neurogenesis; neuropharmacology; neurotransmitter metabolism; neurotrophic factors; newborn animals; nucleic acid probes; peripheral nervous system; radioimmunoassay; substance P; sympathetic nervous system; synapses; tissue /cell culture; tyrosine 3 monooxygenase

The proposed research is an extension of ongoing studies on the plasticity of the nervous system during development, maturity and old age. Using molecular genetic, immunocytochemical, biochemical and pharmacologic techniques, we have found that extracellular signals regulate neurotransmitter metabolism, and may actually alter neurotransmitter phenotypic expression by neurons during development and maturity. We have begun to define trans-synaptic molecular messages and their trophic effects in the neonate and adult nervous system. We are now using in vivo and tissue culture approaches to define the specific molecular messages that govern neurotransmitter plasticity throughout life. The present studies will focus on the molecular mechanisms regulating neuronal plasticity in the peripheral nervous system and brain. More specifically, we hope to a) define molecular genetic mechanisms underlying phenotypic plasticity in neonatal sympathetic neurons, using cDNA probes; b) define the scope and basis of plasticity in adult neurons; c) determine the basis of deficits in plasticity that we have recently defined in aged neurons; d) define molecular genetic mechanisms underlying trans-synaptic regulation of transmitter development, and trans-synaptic regulation of transmitter enzymes during maturity; e) define molecular genetic mechanisms underlying independent regulation of different neurohumoral systems within the same cell, using cDNA to proenkephalin and tyrosine hydroxylase in the adrenal medulla; f) determine how neuronal aggregation alters transmitter phenotypic expression; g) define mechanisms by which nerve growth factor regulates development and maintenance of specific subpopulations of brain neurons, a recent finding in our laboratory. These studies then are directed toward understanding neuronal and synaptic plasticity at the molecular level.

拟议的研究是正在进行的有关可塑性的研究的扩展 在发育，成熟度和老年期间神经系统的。 使用 分子遗传，免疫细胞化学，生化和药理学 技术，我们发现细胞外信号调节 神经递质代谢，实际上可能会改变神经递质 神经元在发育和成熟期间的表型表达。 我们有 开始定义跨突触分子信息及其营养效应 在新生儿和成人神经系统中。 我们现在正在使用体内和 组织培养方法来定义特定分子信息 在一生中控制神经递质的可塑性。 本研究将重点放在调节的分子机制上 周围神经系统和大脑中的神经元可塑性。 更多的 具体而言，我们希望a）定义下面的分子遗传机制 使用cDNA探针，新生儿交感神经元中的表型可塑性； b）定义成人神经元中可塑性的范围和基础； c）确定 我们最近在老年定义的可塑性不足的基础 神经元； d）定义反式突触的基于的分子遗传机制 调节发射机的发育和反式突触调节 成熟期间发射器酶； e）定义分子遗传机制 基本的独立调节在不同的神经肿瘤中 相同的细胞，使用cDNA在卵磷脂和酪氨酸羟化酶中 肾上腺髓质； f）确定神经元聚集如何改变发射器 表型表达； g）定义神经生长因子的机制 调节大脑特定亚群的发展和维护 神经元，我们实验室的最新发现。 这些研究是 致力于理解神经元和突触可塑性 分子水平。