Central Autonomic Control, Aging and Oxidative Stress

描述（由申请人提供）： 专业神经科学研究计划（SNRP）的更新是基于霍华德大学和医学院做出的承诺，这些承诺保证了对培养有才华的少数民族神经科学家目标的长期支持。在SNRP-1期间，我们开发了广泛的研究基础设施，建立了多个跨部门和跨机构的研究合作，并在跨学科研究中实现了重要目标。这些成就对于我们能够吸引三位新的项目负责人参与该计划（SNRP-2）的更新过程至关重要。在SNRP的第一阶段，我们专注于调节呼吸和气道功能的神经元网络，这些神经元网络与参与行为状态控制的系统相耦合。目前的三个相互关联的项目旨在更好地了解神经元网络的结构，功能或遗传改变如何影响心血管功能，衰老和认知。Davila-Garcia博士的项目将使用猫的超微结构、心电图、超声心动图和生理学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。这些新的研究将提供第一个详细的功能作用和神经解剖电路的心室神经节介导迷走神经对心脏的一个或两个心室的影响。由此产生的数据将对了解充血性心力衰竭和肺动脉高压等疾病具有重要意义。Duttaroy博士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的完整性作为年龄的函数。Manaye博士的项目将利用一个成熟的氧化应激小鼠模型，毒性β-淀粉样蛋白（Abeta）的双转基因表达，结合最先进的神经体视学技术，来表征支配杏仁核、海马和额叶皮质的去甲肾上腺素能通路中与年龄和性别相关的改变。这些研究将检验以下假设：与阿尔茨海默病相关的毒性蛋白质的年龄相关积累引起神经炎症反应级联，导致负责认知和情感神经功能的去甲肾上腺素能通路进行性变性。行政核心（核心A）将保持集中的财务记录，编写财务和科学报告，促进共同资源的使用，并监测科学进展。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，生理学和药理学方法的标准化，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。整个计划将提供有关神经元网络可塑性的新知识，这些神经元网络调节自主功能，行为状态控制和认知。

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.