PESTICIDES AND PARKINSONS DISEASE

帕金森病（Parkinson~s disease，PD）的病因尚不清楚，但其发病机制尚不明确， 环境和遗传因素可能会导致 疾病背后的退化过程 结果 流行病学研究表明， 农村地区存在的PD风险和化学品暴露风险 环境，提高了农药可能发挥作用的可能性， PD神经变性 这项建议的目的是筛选一个选定的 农业化学品的数量（就其具体影响而言） 纹状体中的多巴胺能末梢和纹状体中的多巴胺能细胞体 黑质 特别地，联吡啶（百草枯，PQ，敌草快， DQ）氯苯氧基（2，4-二氯苯氧基乙酸，2，4-D）， 有机氯（狄氏剂）、鱼藤碘（鱼藤酮）和硫代氨基甲酸盐 （二乙基二硫代氨基甲酸酯，DDC）化学品的选择是基于 现有的流行病学临床和实验线索 实验 旨在确定这些化合物中是否有任何一种 能够引起多巴胺水平和代谢的变化， 小鼠纹状体和/或黑质。 化学反应也将 通过联合治疗进行评价。 最后，假设 PQ、DQ、2，4-D、狄氏剂、鱼藤酮和/或 DDC在预先损伤的动物中得到促进或增强， 选择性多巴胺能毒物将通过注射这些 1 -甲基-4-苯基-1，2，3，6-四氢吡啶之后的化合物。 这些初步实验的结果将提供急需的 支持或反对农业作用的实验证据 化学物质在PD发病机制中的作用。 呈正相关 测试的农药化合物和多巴胺的变化将构成 发展机械导向研究的基础，以及 有针对性的流行病学研究。

Although the cause of Parkinson~s disease (PD) is unknown, both environmental and genetic factors are likely to contribute to the degenerative process underlying the disease. Results of epidemiological studies suggest an association between an increased risk for PD and ex posure to chemicals present in the rural environment, raising the possibility that pesticides may play a role in PD neurodegeneration. The aim of this proposal is to screen a selected number of agricultural chemicals in terms of their specific effects on dopaminergic terminals in the striatum and dopaminergic cell bodies in the substantia nigra. In particular, bipyridyl (paraquat, PQ, diquat, DQ) chlorophenoxy (2,4-dichlorophenoxyacetic acid, 2,4-D), organochlorine (dieldrin), roteniod (rotenone) and thiocarbamate (diethyldithiocarbamate, DDC) chemicals were chosen based on existing epidemiological, clinical and experimental clues. Experiments are designed to determine whether or not any of these compounds are capable of causing changes in dopamine levels and metabolism in the mouse striatum and/or substantia nigra. Chemical interactions will also be evaluated by combined treatments. Finally, the hypothesis that the neurotoxic properties of PQ, DQ, 2,4-D, dieldrin, rotenone and/or DDC are promoted or enhanced in animals pre-lesioned with a selective dopaminergic toxicant will be tested by injecting these compounds after 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Results of these preliminary experiments will provide much needed experimental evidence in favor of or against a role of agricultural chemicals in the pathogenesis of PD. A positive correlation between the pesticide compounds tested and dopamine changes will constitute the basis for developing mechanistically-oriented research as well as targeted epidemiological studies.