Central Autonomic Control, Aging and Oxidative Stress

中枢自主控制、衰老和氧化应激

• 批准号: 6964597
• 负责人: Vito John Massari
• 金额: $ 147.69万
• 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/6964597
• 关键词: cooperative study; neurochemistry; neuroregulation

DESCRIPTION (provided by applicant): This renewal of the Specialized Neuroscience Research Program (SNRP) is based on commitments made by Howard University and the College of Medicine which guarantee long-term support toward the goal of developing talented minority neuroscientists. During SNRP-1 we 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 to participate 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 three interrelated projects seek to better understand how structural, functional, or genetic alterations in neuronal networks affect cardiovascular functions, aging, and cognition. Dr. Davila-Garcia's Project will use ultrastructural, electrocardiographic, echocardiographic, and physiological methods in the cat to define selected intrinsic cardiac neural mechanisms mediating parasympathetic control of ventricular functions. These novel studies will provide the first detailed analyses of the functional roles and neuroanatomical circuits of ventricular ganglia which mediate vagal effects on either or both ventricles of the heart. The resulting data will have important implications for understanding diseases such as congestive heart failure and pulmonary hypertension. The overall goal of Dr. Duttaroy's Project 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. Dr. Manaye's Project will utilize a well established mouse model of oxidative stress, the double transgenic expression of toxic beta-amyloid (Abeta), in combination with state-of the-art neurostereological techniques, 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. Administrative Core (Core A) will maintain centralized financial record keeping, prepare financial and scientific reports, facilitate the use of common resources, and monitor scientific progress. Neurobiology Core 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 proposal for renewal arises directly from on-going work in our laboratories at Howard University. The overall program will provide new knowledge on plasticity of neuronal networks that regulate autonomic functions, behavioral state control, and cognition.

描述（由申请人提供）： 该专业神经科学研究计划（SNRP）的这种续签是基于霍华德大学和医学院做出的承诺，这些承诺可以保证长期支持发展才华横溢的少数族裔神经科学家。在SNRP-1期间，我们开发了广泛的研究基础设施，建立了多个部门间和机构间研究合作，并在跨学科研究中实现了重要的目标。这些成就对于我们能够吸引三个新项目负责人参加该计划的续签（SNRP-2）的过程至关重要。在SNRP的第一阶段中，我们专注于调节呼吸的神经元网络和与行为状态控制有关的系统耦合的气道功能。当前的三个相互关联的项目旨在更好地理解神经元网络中的结构，功能或遗传改变如何影响心血管功能，衰老和认知。 Davila-Garcia博士的项目将使用CAT中的超微结构，心电图，超声心动图和生理方法来定义介导心室功能副交感神经控制的选定内在心脏神经机制。这些新的研究将对心室神经节的功能作用和神经解剖回路进行首次详细分析，这些分析介导了对心脏的任何一个或两个心室的迷走神经作用。最终的数据将对理解诸如充血性心力衰竭和肺动脉高压等疾病具有重要意义。杜塔罗伊（Duttaroy）项目项目的总体目标是使用果蝇模型来了解氧化损伤保护系统的机理基础，以及如何致力于维持神经系统的完整性，认知和神经肌肉能力作为年龄的函数。 Manaye博士的项目将利用良好的氧化应激模型，毒性β-淀粉样蛋白（ABETA）的双转基因表达，以及最新的神经素学技术，以年龄和性别相关的变化来表征非肾上腺素途径的变化。这些研究将检验以下假设：与阿尔茨海默氏病有关的有毒蛋白与年龄相关的毒物积累导致一系列神经炎症反应，导致造成认知和情感神经功能的去甲肾上腺素能途径的逐渐退化。行政核心（核心A）将保持集中的财务记录，准备财务和科学报告，促进使用共同资源并监控科学进步。神经生物学核心将提供中央设施，促进解剖学，神经化学，分子，生理和药理方法的标准化，并确保数据分析的统一标准。此续签提案中的每个项目都直接源于我们在霍华德大学实验室正在进行的工作。整个程序将提供有关调节自主功能，行为状态控制和认知的神经元网络可塑性的新知识。