NEUROMORPHOLOGY AND SUBCELLULAR STRUCTURE IN AGING

本研究项目的长期目标是确定 关键因素是负责老化过程中的神经 系统 鉴于衰老过程中最关键的事件之一是 神经元的持续死亡和传入神经阻滞，我们将解决因素 导致了这次的死亡 细胞死亡一直是 归因于兴奋性毒性，导致自我毁灭， 细胞内游离钙超载。 有待检验的假设是， 质膜分子亚结构数量和定位 并且内质网在衰老过程中发生改变。 本研究 建议评估浦肯野细胞树突状细胞的形态计量学参数 膜通道和钙螯合细胞器的结构， 动物群体之间的差异。 正常动物记录的值 将与老年大鼠综合征模型（AS）的那些进行比较， 加速综合征模型（AAS）和急性细胞死亡模型。 上 作为研究的一部分，我们将对免疫标记的 树突状细胞上的钙内流位点，以确定是否有 是这些通道的位置和相对数量的变化 准备工作之间。 用抗体标记P通道将显示 这些渠道的分布和密度。 三维分析 将免费进行树突的定量生理结果 钙分布（项目Ia）到隔室，以与 P通道在树突上的分布。 第二部分 研究中，我们将定位细胞内钙螯合位点， 可能的释放区与特定的隔室相关联 内质网 树突被兴奋性毒素改变，或加速 将老化与老年大鼠的老化进行比较，以确定 细胞内膜参数和通道的位置以及螯合 大分子可以在每个模型系统内改变。 结果 从形态学研究中获得的数据将与 导致细胞死亡的因素的生理和生化分析，或 修剪连接。

The long-term objective of this research project is to determine what pivotal factors are responsible for the aging process in the nervous system. Given that one of the most critical events in aging is the continuous death and deafferentation of neurons, we will address factors leading to this demise. Cell death has been attributed to excitotoxicity resulting in self-destruction due to an overloading of free cytosolic calcium. The hypothesis to be tested is that the amount and localization of molecular substructure of plasma membranes and endoplasmic reticulum is altered in aging processes. This study proposed to evaluate morphometric parameters of Purkinje cell dendritic architecture for membrane channels and calcium sequestering organelles for differences between animal groups. Values recorded from normal animals will be compared to those for an aged rat syndrome model (AS), an age accelerated syndrome model (AAS) and acute cell death models. In the first part of the study, we will localize morphometrically the immunolabeled calcium influx sites on dendritic compartments to determine whether there are shifts in the location and the relative number of these channels between preparations. Labelling of P channels with antibodies will show the distribution and density of these channels. Three-dimensional analysis of dendrites will be performed to quantitate physiological results for free calcium distribution (Project Ia) into compartments for comparison with the P channel distribution over the dendrites. In the second part of the study, we will localize intracellular calcium sequestering sites and possible release zones associated with specific compartments of the endoplasmic reticulum. Dendrites altered by excitotoxins, or accelerated aging will be compared to those from aged rats to determine how the intracellular membrane parameters and location of channels and sequestering macromolecules may be altered within each model system. The results obtained from morphological studies will be evaluated together with physiological and biochemical analyses for factors leading to cell death or pruning of connections.