NEUROMORPHOLOGY AND SUBCELLULAR STRUCTURE IN AGING

这项研究项目的长期目标是确定 神经衰老过程中的关键因素 系统。鉴于老龄化中最关键的事件之一是 神经元的持续死亡和去传入，我们将解决这些因素 导致了这场死亡。细胞死亡一直是 归因于兴奋毒性导致的自毁，由于 胞浆游离钙超载。需要检验的假设是 质膜分子亚结构的数量和定位 内质网在衰老过程中发生改变。本研究 普肯野细胞树突状细胞形态计量学参数的研究 膜通道和钙隔离细胞器的体系结构 动物群体之间的差异。从正常动物记录的数值 将与老年大鼠综合征模型(AS)进行比较， 加速综合征模型(AAS)和急性细胞死亡模型。在第一个 作为研究的一部分，我们将对免疫标记的 树突室上的钙内流部位确定是否有 是这些通道的位置和相对数量的变化 在两次准备之间。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 将免费执行树枝状结构以量化生理结果 钙分配(项目Ia)进入隔间，以与 P通道在树突上的分布。在第二部分中， 研究中，我们将定位细胞内钙离子隔离位置和 可能的释放区与特定隔间相关联 内质网。被刺激性毒素改变或加速的树突 衰老将与衰老大鼠的衰老进行比较，以确定 细胞内膜参数与通道和隔离的位置 在每个模型系统中，大分子可能会发生变化。结果是 从形态研究中获得的信息将与 细胞死亡或死亡因素的生理生化分析 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.