SPACE FLIGHT, STRESS, AND NEURONAL PLASTICITY

描述：（改编自申请人摘要） 据报道，神经元功能与长期停留有关 在微重力环境下。 尽管可能会产生一些相关性， 在太空中长时间停留的代谢效应，这些机制 不能很容易地用来解释神经系统的具体变化 功能 在细胞中对神经元动力学的系统检查 需要从分子水平来理解 微重力可能导致神经功能受损。 的 本申请中的实验将为定义 神经元可塑性、连通性和 功能 将特别注意确定监管 可用于改善或减少潜在的 神经系统中与延长阶段相关的有害变化 在太空 将讨论两个具体目标：1）确定 空间飞行对动力学、组织和组成的影响 神经细胞骨架的结构。 神经元功能的长期变化 据报告，在空间环境中长期停留后， 细胞骨架元素形成神经元的结构基础 架构和动力学。 由于组成和 神经元结构和再生的组织， 神经元群体的可塑性与神经元的动力学密切相关。 细胞骨架 特定的属性似乎是局部调制的， 轴突的微环境和与靶细胞的相互作用，所以 太空飞行的条件可能会对神经元的连接产生不利影响 和可塑性通过几种机制，包括模式的变化， 以及轴突微环境的改变 与微重力或压力有关。 为此目的的实验是 旨在描述太空飞行对轴突的影响， 细胞骨架和识别潜在的机制。 2）。 评价 突触前末梢小泡运输的分子机制 对神经元可塑性和突触传递很重要。 持续 神经递质的释放需要囊泡的精确协调 运动，细胞器的定位，膜蛋白的分选， 快速轴突运输的转向和突触囊泡的再循环 选民。 虽然在这方面取得了相当大的进展， 了解一些相关的分子机制，如快速 轴突运输，相对较少的是知道的分子 与囊泡运输有关的信号、马达或分类机械 在突触前末梢 囊泡循环的改变可能 影响突触末端的维持和连接的稳定性 通过营养相互作用的丧失或信号传导的中断 通过轴突运输介导的通路。 为此目的的实验是 旨在确定控制囊泡运输的分子机制 并确定可能受条件影响的中间体 of space空间flight飞行.

DESCRIPTION: (Adapted from Applicant's Abstract) Long-term changes in neuronal function have been reported in connection with extended stays in a microgravity environment. Although some correlations may be made with metabolic effects of extended stays in space, these mechanisms cannot readily be used to explain specific changes in nervous system function. A systematic examination of neuronal dynamics at the cellular and molecular level is needed to understand how extended exposure to microgravity can result in compromised neuronal function. The experiments in this application will provide a basis for defining the molecular basis for changes in neuronal plasticity, connectivity, and function. Particular attention will be paid to identifying regulatory pathways which may be used to ameliorate or reduce potentially deleterious changes in the nervous system associated with extended stages in space. Two specific aims will be addressed: 1) To determine the effects of space flight on the dynamics, organization, and composition of the neuronal cytoskeleton. Long-term changes in neuronal function have been reported following extended stays in a space environment. Cytoskeletal elements form the structural basis for neuronal architecture and dynamics. Since changes in the composition and organization of the neuronal architecture and regeneration, the plasticity of a neuronal population is closely linked to dynamics of the cytoskeleton. Specific properties appear to be locally modulated by the microenvironment of the axon and interactions with target cells, so the conditions of space flight may adversely affect neuronal connectivity and plasticity through several mechanisms, including changes in patterns of synaptic activity, and alterations in the axonal microenvironment associated with microgravity or stress. Experiments in this aim are designed to characterize the effects of space flight on the axonal cytoskeleton and identify underlying mechanisms. 2). To evaluate molecular mechanisms of vesicle trafficking in the presynaptic terminal important for neuronal plasticity and synaptic transmission. Sustained release of neurotransmitter requires precise coordination of vesicle movements, targeting of organelles, sorting of membrane proteins, turnaround of fast axonal transport, and recycling of synaptic vesicle constituents. While considerable progress has been made toward understanding some of the associated molecular mechanisms such as fast axonal transport, relatively little is known about the molecular signals, motors, or sorting machinery associated with vesicle trafficking in the presynaptic terminal. Alterations in vesicle recycling may affect maintenance of synaptic terminals and stability of connections through a loss of trophic interactions or disruption of signalling pathways mediated through axonal transport. Experiments in this aim are designed to define molecular mechanisms that control vesicle trafficking and to identify intermediates that might be affected by the conditions of space flight.