Central Autonomic Control, Aging and Oxidative Stress

中枢自主控制、衰老和氧化应激

• 批准号: 7497293
• 负责人: Vito John Massari
• 金额: $ 4.1万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497293
• 关键词: Academia; Achievement; Advertising; Affect; Affective; Age; Aging; Alzheimer' s Disease; Amygdaloid structure; Amyloid; Anatomy; Applications Grants; Area; Autoradiography; Behavioral; Biochemistry; Biological; Biology; Breathing; Cardiovascular Physiology; Cardiovascular system; Chronic; Clinic; Clinical; Cognition; Cognitive; Collaborations; Communication; Communities; Complement; Computers; Condition; Core Facility; Coupled; Data Analyses; Depth; Discipline; District of Columbia; Doctor of Philosophy; Down-Regulation; Drosophila genus; Education; Educational process of instructing; Engineering; Enrollment; Environment; Exposure to; Faculty; Felis catus; Female; Ferrets; Financial Support; Fostering; Functional disorder; Funding; Future; Ganglia; Gender; Genetic; Geographic Locations; Goals; Graduate Education; Grant; Heart Ventricle; Hippocampus (Brain); Human Resources; Hyperactive behavior; Hypoxia; Industry; Institution; Interdisciplinary Study; Interest Group; Internships; Joints; Journals; Knowledge; Laboratories; Lead; Lung; Maryland; Mathematics; Mediating; Medicine; Mentorship; Methods; Michigan; Minority; Mission; Modeling; Molecular; Monitor; Myxoid cyst; Nervous System Physiology; Nervous system structure; Neurobiology; Neurons; Neurophysiology - biologic function; Neurosciences; Neurosciences Research; Nonprofit Organizations; Occupations; Online Systems; Oxidative Stress; Oxygen; Paper; Participant; Pathway interactions; Peer Review; Pharmacology; Phase; Philosophy; Physics; Physiological; Physiology; Pliability; Population; Postdoctoral Fellow; Preparation; Prevention; Process; Proteins; Publications; Published Comment; Publishing; Rate; Recruitment Activity; Regulation; Reporting; Research; Research Activity; Research Infrastructure; Research Personnel; Resources; Right Ventricular Function; Right ventricular structure; Schools; Science; Scientist; Selection Criteria; Source; Standardization; Structure; Students; Suggestion; Support of Research; System; Techniques; Testing; Training; Training Programs; Transgenic Organisms; Translating; Treatment Protocols; United States National Institutes of Health; Universities; University Hospitals; Week; Wisconsin; Woman; Work; Workplace; Writing; age related; airway hyperresponsiveness; base; career; college; deprivation; design; drug development; editorial; environmental change; experience; frontal lobe; high school; improved; interdisciplinary approach; interest; medical schools; nervous system disorder; neurochemistry; neuromechanism; news; noradrenergic; novel strategies; originality; outreach program; programs; receptor; relating to nervous system; respiratory; response; size; success; symposium; teacher

This renewal of the Specialized Neuroscience Research Program (SNRP) is based on commitments made by Howard University and the College of Medicine, in guaranteeing long-term support toward the goal of developing talented minority neuroscientists. During SNRP-1 we have developed an extensive research infrastructure, established multiple inter-departmental and inter-institutional research collaborations, and accomplished significant goals in interdisciplinary research. These achievements were crucial to the process by which we were able to attract three new project leaders in the renewal of this program, (SNRP-2). In phase one of the SNRP, we focused on neuronal networks regulating breathing and the airway functions that are coupled to systems involved in behavioral state control. The current four interrelated projects seek to better understand how environmental changes, aging, and genetic factors lead to dynamic structural and functional alterations in the networks that affect respiratory and cardiovascular functions, and cognition. Project 1 will use ultrastructural, molecular biological, and physiological approaches to define central mechanisms involved in chronic intermittent hypoxia-induced airway hyper-reactivity. In the ferret model, it will test the hypothesis that repeated short-term oxygen deprivation (oxidative stress) enhances the central excitatory neural inputs upon airway-related vagal preganglionic neurons (AVPNs) through down regulation of GABAergic and monoaminergic (serotonergic and noradrenergic) inhibitory influences, leading to a hyperexcitable state of these AVPNs and to airway hyperactivity. Project 2 will use ultrastructural, electrocardiographic, echocardiographic, and physiological methods to define selected neural mechanisms mediating cardio-pulmonary integration. The cat model will be used to study the parasympathetic regulation of right ventricular functions . Namely, it will examine the extrinsic nervous control of the interventriculo-septal (IVS) ganglion, neurons of which provide the major source of vagal postganglionic terminals innervating the right ventricle of the heart. The function of these neurons can be affected by oxidative stress as a consequence of pathological conditions that in turn enhances cardiovascular dysfunctions. The overall goal of Project 3 is to use the Drosophila model to understand the mechanistic basis of an oxidative damage protection system and how it is devoted towards maintaining the integrity of the nervous system, cognition, and neuromuscular ability as a function of age. Project 4 will utilize a well established model of oxidative stress, the double transgenic expression of toxic g-amyloid (AB), in combination with state-of theart neurostereological techniques and quantitative receptor autoradiography, to characterize age- and gender-related alterations in noradrenergic pathways innervating the amygdala, hippocampus, and frontal cortex. These studies will test the hypothesis that the age-related accumulation of toxic proteins related to Alzheimer's disease cause a cascade of neuroinflammatory responses leading to progressive degeneration of noradrenergic pathways responsible for cognitive and affective neurological functions. Core A will maintain centralized financial record keeping, prepare financial and scientific reports, facilitate the use of common resources, and monitor scientific progress. Core B will provide central facilities, facilitate standardization of anatomical, neurochemical, molecular, physiological, and pharmacological methods, and assure uniform criteria for data analysis. Each project in this renewal proposal arises directly from on-going work in our laboratories at Howard University. The overall program will provide new knowledge on plasticity of central networks that regulate autonomic functions, behavioral state control, and cognition.

专业神经科学研究计划（SNRP）的更新是基于以下方面的承诺： 霍华德大学和医学院，在保证长期支持的目标，发展 有才华的少数民族神经学家在SNRP-1期间，我们建立了广泛的研究基础设施， 多个跨部门和跨机构的研究合作，并完成了重大目标， 跨学科研究这些成就对于我们能够吸引三个新的 项目负责人在该计划的更新，（SNRP-2）。在SNRP的第一阶段，我们专注于神经元 调节呼吸和气道功能的网络，这些网络与参与行为状态的系统相耦合 控制目前的四个相互关联的项目寻求更好地了解环境变化，老龄化， 遗传因素导致影响呼吸系统的网络中的动态结构和功能改变， 心血管功能和认知能力项目1将使用超微结构，分子生物学和生理学 定义慢性间歇性缺氧诱导的气道高反应性的中枢机制的方法。在 雪貂模型，它将测试的假设，反复短期缺氧（氧化应激）增强 中枢兴奋性神经输入通过下调作用于气道相关迷走神经节前神经元 GABA能和单胺能（肾上腺素能和去甲肾上腺素能）抑制作用，导致过度兴奋 这些AVPN的状态和气道过度活跃。项目2将使用超微结构，心电图， 超声心动图和生理学方法来定义介导心肺功能的选定神经机制 一体化猫模型将用于研究右心室功能的副交感神经调节。 也就是说，它将检查室间隔（IVS）神经节的外在神经控制，其中神经元 提供支配心脏右心室的迷走神经节后末梢的主要来源。的功能 这些神经元可以受到氧化应激的影响，这是病理条件的结果， 心血管功能障碍项目3的总体目标是使用果蝇模型来理解 氧化损伤保护系统的机制基础，以及它如何致力于维持 神经系统、认知和神经肌肉能力作为年龄的函数。项目4将利用完善的 氧化应激模型，毒性g-淀粉样蛋白（AB）的双转基因表达，结合现有技术， 神经体视学技术和定量受体放射自显影，以表征年龄和性别相关的 神经支配杏仁核、海马和额叶皮质的去甲肾上腺素能通路的改变。这些研究将 测试与阿尔茨海默病相关的毒性蛋白质的年龄相关积累引起级联反应的假设 神经炎症反应导致去甲肾上腺素能通路的进行性变性， 认知和情感神经功能。核心A将保持集中的财务记录， 财务和科学报告，促进共同资源的使用，并监测科学进展。核心B将 提供中心设施，促进解剖学、神经化学、分子、生理学和 药理学方法，并确保数据分析的统一标准。 本更新提案中的每个项目都直接来自我们霍华德大学实验室正在进行的工作。 整个计划将提供关于调节自主神经的中枢网络可塑性的新知识 功能、行为状态控制和认知。