PATHOGENEIS OF NEUROTOXIC DISEASE: CELL BODY AND AXON

神经毒性疾病的发病机制：细胞体和轴突

基本信息

批准号：
3250855
负责人：
ARNOLD B STERMAN
金额：
$ 10.43万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-05-01 至 1986-03-31
项目状态：
已结题

项目摘要

The most common clinico-pathologic manifestation of exposure to environmental neurotoxins is degeneration of long and large nerve fibers (axons). Most research on these diseases during the past decade has addressed the degenerating nerve fiber; little interest has focused on the nerve cell body (soma), despite its established role in maintaining and repairing the axon. My initial studies in intoxicated rats have shown a spectrum of morphologic changes, suggesting an orchestrated pattern of cell body remodeling. The current five year proposal is directed towards understanding how cell body remodeling and cell body-axon interactions act to determine the fate of intoxicated neurons. Secondarily, it will help provide the scientific basis for screening pollutants for neurotoxicity, and provide information about the basic biology of chromatolysis. Experimental rats will be intoxicated with the prototype neurotoxins 2,5-hexanedione and acrylamide monomer to study axons and cell bodies using quantitated light and electron microscopy, autoradiography, and histofluorescence techniques. A first set of experiments will study motoneurons and dorsal root ganglion neurons in relation to axonal degeneration. It will address the specificity and early evolution of cell body remodeling and correlate this with autoradiographic data on RNA and protein metabolism. A second set of experiments will study cell body and axon changes in identified portions of the sympathetic (autonomic) nervous system. Investigation will focus on questions of specific vulnerability and the pattern of cell body-axon changes; morphologic changes will be correlated with metabolic data on RNA and protein synthesis, and with histofluorescent investigation of neurotransmitter in cell body and axon.

暴露于环境中最常见的临床病理表现环境神经毒素是长而大的神经纤维的退化（轴突）。过去十年对这些疾病的大多数研究解决退化的神经纤维；很少有兴趣集中在神经细胞体（soma），尽管它在维持和维持神经细胞体方面发挥着既定的作用修复轴突。我对中毒老鼠的初步研究表明形态变化的范围，表明细胞的精心设计的模式身体重塑。目前的五年提案旨在了解细胞体重塑和细胞体轴突相互作用如何发挥作用确定中毒神经元的命运。其次，它会有所帮助为筛选污染物的神经毒性提供科学依据，并提供有关色谱分离的基本生物学信息。实验大鼠将因原型神经毒素而中毒 2,5-己二酮和丙烯酰胺单体用于研究轴突和细胞体定量光学和电子显微镜、放射自显影术和组织荧光技术。第一组实验将研究运动神经元和背根神经节神经元与轴突的关系退化。它将解决细胞的特异性和早期进化问题身体重塑并将其与 RNA 和放射自显影数据相关联蛋白质代谢。第二组实验将研究细胞体和交感（自主）神经的确定部分的轴突变化系统。调查将集中于特定漏洞的问题以及细胞体轴突变化的模式；形态变化将是与 RNA 和蛋白质合成的代谢数据相关，并与细胞体和轴突中神经递质的组织荧光研究。