Central Autonomic Control, Aging and Oxidative Stress

描述(由申请人提供)： 此次更新的专门神经科学研究计划(SNRP)是基于霍华德大学和医学院做出的承诺，这些承诺保证对培养有才华的少数族裔神经科学家的目标提供长期支持。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协作，并实现了跨学科研究的重要目标。这些成就对于我们能够吸引三名新的项目负责人参与该计划(SNRP-2)的续签进程至关重要。在SNRP的第一阶段，我们专注于调节呼吸的神经网络和与参与行为状态控制的系统耦合的呼吸道功能。目前的三个相互关联的项目试图更好地了解神经网络中的结构、功能或遗传变化如何影响心血管功能、衰老和认知。Davila-Garcia博士的项目将在猫身上使用超微结构、心电图学、超声心动图和生理学方法来确定介导副交感神经控制心脏功能的选定的内在心脏神经机制。这些新颖的研究将首次详细分析脑室神经节的功能作用和神经解剖回路，它介导了迷走神经对心脏一个或两个脑室的影响。由此得出的数据将对理解充血性心力衰竭和肺动脉高压等疾病具有重要意义。达塔罗伊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博士的项目将利用一个成熟的氧化应激小鼠模型，即毒性β-淀粉样蛋白(Abeta)的双重转基因表达，结合最先进的神经体视学技术，来表征杏仁核、海马体和额叶皮质去甲肾上腺素能通路中与年龄和性别相关的变化。这些研究将检验这一假设，即与阿尔茨海默病相关的有毒蛋白的年龄相关积累会引起一系列神经炎性反应，导致负责认知和情感神经功能的去甲肾上腺素能通路的进行性退化。行政核心(核心A)将保持集中的财务记录保存，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。神经生物学核心公司将提供中央设施，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。这项更新建议中的每个项目都直接源于我们在霍华德大学的实验室正在进行的工作。整个课程将提供有关调节自主神经功能、行为状态控制和认知的神经网络可塑性的新知识。

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.