PESTICIDES AND PARKINSONS DISEASE

农药与帕金森病

• 批准号: 2019052
• 负责人: DONATO A DI MONTE
• 金额: $ 7.66万
• 依托单位: PARKINSON'S INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-10-28 至 1998-10-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019052
• 关键词: Parkinson's disease; chlorohydrocarbon insecticide; disease /disorder etiology; dopamine; environmental toxicology; high performance liquid chromatography; insecticides; laboratory mouse; methylphenyltetrahydropyridine; neurotransmitter metabolism; pesticide biological effect; serotonin

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.

虽然帕金森氏症（PD）的病因尚不清楚

项目成果

Cerebrospinal fluid 3,4-dihydroxyphenylacetic acid level after tolcapone administration as an indicator of nigrostriatal degeneration.

托卡朋给药后脑脊液 3,4-二羟基苯乙酸水平作为黑质纹状体变性的指标。

• DOI: 10.1016/s0014-4886(03)00140-7
• 发表时间: 2003
• 期刊: Experimental neurology
• 影响因子: 5.3
• 作者: Thiffault,Christine;Langston,JWilliam;DiMonte,DonatoA
• 通讯作者: DiMonte,DonatoA

Ethylenebisdithiocarbamate enhances MPTP-induced striatal dopamine depletion in mice.

亚乙基双二硫代氨基甲酸酯增强 MPTP 诱导的小鼠纹状体多巴胺消耗。

• 发表时间: 2000
• 期刊: Neurotoxicology.
• 作者: McGrew,DM;Irwin,I;Langston,JW
• 通讯作者: Langston,JW

Applications and technical challenges of fluorescence in situ hybridization in stem cell research.

荧光原位杂交在干细胞研究中的应用和技术挑战。

• DOI: 10.1016/j.bcmd.2003.09.017
• 发表时间: 2004
• 期刊: Blood cells, molecules & diseases
• 作者: Weier,Heinz-UlliG;Chu,LisaW;Murnane,JohnP;Weier,JinglyF
• 通讯作者: Weier,JinglyF