AXONAL CYTOSKELETON AND TRANSPORT IN IDPN INTOXICATION

这项建议的目的是研究贝塔病毒的发病机制， β‘-亚氨基二丙腈(IDPN)模型及其应用在……里面 经IDPN处理的大鼠，神经丝蛋白转运严重 损害，而快速顺行和逆行传输率 不受影响；同时，轴浆细胞器的重组 神经细丝向外移位的地方 微管、线粒体和平滑内质网 轴突中心。使用过氧化物酶-抗过氧化物酶技术和 抗微管相关微管蛋白的亲和纯化多克隆抗体 蛋白2(MAP2)和tau因子，抗微管蛋白，MAP2， 肌动蛋白、肌球蛋白、原肌球蛋白，可能还有tau因子，以及一种针对 神经细丝的68,000个道尔顿亚基轴突的组织 大鼠细胞骨架和鸡胚期运动神经元的培养 IDPN后光镜和电子显微镜水平的观察 行政管理。作为IDPN模型的一个应用，我们将研究 逆行转运蛋白轴突分布的定量研究 (2，3-~3H)N-琥珀酰亚胺共价标记后的电子自显影 丙酸在对照组和IDPN大鼠中的作用 微管和其他细胞器在逆行运输中 已经为快速顺行运输做好了准备。神经丝状物 积聚、继发性脱髓鞘和胶质增生类似于 在IDPN中发现的中毒也在人类的各种代谢和 退行性疾病、中毒、痴呆等。逆行运输 是一个基本的神经元过程，与生长、维持、 神经元的再生和病理(例如破伤风、脊髓灰质炎、 糖尿病神经病变，吡啶硫酮锌引起的垂死性神经病变， 等)。通过建议的研究，我们希望能更好地了解不同的 轴突细胞骨架组成成分之间的相互作用及其机制(S) 轴浆转运，它的错乱可能是许多 神经系统疾病。

The aim of this proposal is to study the pathogenesis of the Beta, Beta'-iminodipropionitrile (IDPN) model and some of its applications. In IDPN-treated rats, the transport of neurofilament proteins is severely impaired, while the rates of fast anterograde and retrograde transports are not affected; concurrently, a reorganization of axoplasmic organelles takes place with displacement of neurofilaments towards the periphery and of microtubules, mitochondria and smooth endoplasmic reticulum towards the center of axons. Using the peroxidase-antiperoxidase technique and affinity purified polyclonal antibodies to tubulin, microtubule-associated protein 2 (MAP2) and tau factor, monoclonal antibodies to tubulin, MAP2, actin, myosin, tropomyosin, and possibly tau factor, and an antiserum to the 68,000 dalton subunit of neurofilament the organization of axonal cytoskeleton in rats and embryonal chicken motor neurons in culture will be investigated at the light and electron microscope (EM) level following IDPN administration. As an application of the IDPN model, we will study the axonal distribution of proteins of retrograde transport with quantitative EM autoradiography after covalent labelling with (2,3-3H) N-succinimidyl propionate in control and IDPN rats in order to investigate the role of microtubules and other organelles in retrograde transport as we have already done for the fast anterograde transport. Neurofilamentous accumulations, secondary demyelination and gliosis similar to the ones found in IDPN intoxications are also seen in various human metabolic and degenerative dieases, intoxications, dementias, etc. Retrograde transport is a basic neuronal process involved with the growth, maintenance, regeneration and pathology of neurons (e.g., tetanus, poliomyelitis, diabetic neuropathy, dying-back neuropathy caused by zinc pyridinethione, etc.). With the proposed studies we hope to better understand the various interactions among the components of axonal cytoskeleton and mechanism(s) of axoplasmic tranport, derangement of which might be the key to so many neurological diseases.