Department of Biology, King College, Bristol, TN 37620, USA.
Neurotoxicology. 2011 Jun;32(3):331-41. doi: 10.1016/j.neuro.2011.02.002. Epub 2011 Mar 3.
Epidemiological evidence suggests positive correlations between pesticide usage and the incidence of Parkinson's disease (PD). To further explore this relationship, we used wild type (N2) Caenorhabditis elegans (C. elegans) to test the following hypothesis: Exposure to a glyphosate-containing herbicide (TD) and/or a manganese/zinc ethylene-bis-dithiocarbamate-containing fungicide (MZ) may lead to neurotoxicity. We exposed N2 worms to varying concentrations of TD or MZ for 30 min (acute) or 24h (chronic). To replicate agricultural usage, a third population was exposed to TD (acute) followed by MZ (acute). For acute TD exposure, the LC(50)=8.0% (r(2)=0.6890), while the chronic LC(50)=5.7% (r(2)=0.9433). Acute MZ exposure led to an LC(50)=0.22% (r(2)=0.5093), and chronic LC(50)=0.50% (r(2)=0.9733). The combined treatment for TD+MZ yielded an LC(50)=12.5% (r(2)=0.6367). Further studies in NW1229 worms, a pan-neuronally green fluorescent protein (GFP) tagged strain, indicated a statistically significant (p<0.05) and dose-dependent reduction in green pixel number in neurons of treated worms following each paradigm. This reduction of pixel number was accompanied by visual neurodegeneration in photomicrographs. For the dual treatment, Bliss analysis suggested synergistic interactions. Taken together, these data suggest neuronal degeneration occurs in C. elegans following treatment with environmentally relevant concentrations of TD or MZ.
流行病学证据表明，农药使用与帕金森病（PD）的发病率之间存在正相关关系。为了进一步探讨这种关系，我们使用野生型（N2）秀丽隐杆线虫（C. elegans）来检验以下假设：暴露于含草甘膦的除草剂（TD）和/或含锰/锌乙撑双二硫代氨基甲酸盐的杀菌剂（MZ）可能导致神经毒性。我们将 N2 线虫暴露于不同浓度的 TD 或 MZ 中 30 分钟（急性）或 24 小时（慢性）。为了复制农业用途，第三组线虫先暴露于 TD（急性），然后暴露于 MZ（急性）。对于急性 TD 暴露，LC(50)=8.0%（r(2)=0.6890），而慢性 LC(50)=5.7%（r(2)=0.9433）。急性 MZ 暴露导致 LC(50)=0.22%（r(2)=0.5093），慢性 LC(50)=0.50%（r(2)=0.9733）。TD+MZ 的联合处理导致 LC(50)=12.5%（r(2)=0.6367）。在 NW1229 线虫中的进一步研究中，一种全神经元绿色荧光蛋白（GFP）标记的品系，表明在每种方案后，处理过的线虫神经元中的绿色像素数量呈统计学上显著（p<0.05）和剂量依赖性减少。这种像素数量的减少伴随着光镜照片中的视觉神经退行性变。对于双重处理， Bliss 分析表明存在协同相互作用。总之，这些数据表明，在 C. elegans 中，用环境相关浓度的 TD 或 MZ 处理后会发生神经元退化。
