SPACE FLIGHT, STRESS, AND NEURONAL PLASTICITY

描述：(改编自申请者摘要)长期变化 据报道，神经功能与长时间停留有关 在微重力环境中。尽管可能会有一些关联 随着长时间停留在太空的新陈代谢影响，这些机制 不能轻易地用来解释神经系统的具体变化 功能。对细胞内神经元动力学的系统检查 需要分子水平才能理解延长接触时间 微重力会导致神经元功能受损。这个 此应用程序中的实验将为定义 神经元可塑性、连通性和神经功能改变的分子基础 功能。将特别注意确定监管机构 可用于潜在地改善或减少的途径 与分期延长相关的神经系统的有害变化 在太空中。将解决两个具体目标：1)确定 太空飞行对动力学、组织和组成的影响 神经元细胞骨架的。神经功能的长期变化 据报道，这是在空间环境中长期停留后发生的。 细胞骨架元素构成神经元的结构基础 建筑和动力学。由于构图的变化和 神经元结构和再生的组织， 神经元群体的可塑性与神经细胞的动力学密切相关 细胞骨架。特定属性似乎是由 轴突的微环境以及与靶细胞的相互作用，因此 太空飞行条件可能会对神经元连接产生不利影响 和可塑性，通过几种机制，包括模式的变化 突触活动和轴突微环境的改变 与微重力或压力有关。这一目标的实验是 旨在描述太空飞行对轴突的影响 细胞骨架和确定潜在的机制。2)。评估 突触前终末小泡运输的分子机制 对神经元的可塑性和突触传递很重要。持续期 神经递质的释放需要囊泡的精确协调 运动，细胞器的定位，膜蛋白的分类， 快速轴突运输的转机和突触小泡的再循环 选民。虽然已经在以下方面取得了相当大的进展 了解一些相关的分子机制，如FAST 轴突运输，对分子的了解相对较少 与水泡运输有关的信号、马达或分拣机械 在突触前终末。囊泡回收的变化可能 影响突触终末的维持和连接的稳定性 通过营养相互作用的丧失或信号的中断 通过轴突运输调节的通路。这一目标的实验是 旨在定义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 太空飞行的一部分。

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.