Department of Biology, King College, 1350 King College Road, Bristol, TN 37620, USA.
Neurotox Res. 2012 Apr;21(3):281-90. doi: 10.1007/s12640-011-9274-7. Epub 2011 Sep 16.
Previous studies demonstrate a positive correlation between pesticide usage and Parkinson's disease (PD), which preferentially targets dopaminergic (DAergic) neurons. In order to examine the potential relationship between two common pesticides and specific neurodegeneration, we chronically (24 h) or acutely (30 min) exposed two Caenorhabditis elegans (C. elegans) strains to varying concentrations (LC(25), LC(50) or LC(75)) of TouchDown(®) (TD) as percent active ingredient (glyphosate), or Mancozeb(®) (MZ) as percent active ingredient (manganese/zinc ethylene-bis-dithiocarbamate). Furthermore, to more precisely model environmental exposure, worms were also exposed to TD for 30 min, followed by 30-min incubation with varying MZ concentrations. Previous data from out lab suggested general neuronal degeneration using the worm strain NW1229 (pan-neuronal//green fluorescent protein (GFP) construct). To determine whether distinct neuronal groups were preferentially affected, we specifically used EG1285 (GABAergic neurons//GFP construct) and BZ555 (DAergic neurons//GFP construct) worms to verify GABAergic and DAergic neurodegeneration, respectively. Results indicated a statistically significant decrease, when compared to controls (CN), in number of green pixels associated with GABAergic neurons in both chronic (*P < 0.05) and acute (*P < 0.05) treatment paradigms. Analysis of the BZ555 worms indicated a statistically significant decrease (*P < 0.05) in number of green pixels associated with DAergic neurons in both treatment paradigms (chronic and acute) when compared to CN. Taken together, our data suggest that exposure to TD and/or MZ promotes neurodegeneration in both GABAergic and DAergic neurons in the model organism C. elegans.
先前的研究表明，农药的使用与帕金森病（PD）之间存在正相关关系，PD 优先针对多巴胺能（DAergic）神经元。为了研究两种常见农药与特定神经退行性疾病之间的潜在关系，我们用不同浓度的 TouchDown（TD）（按有效成分计为草甘膦）或 Mancozeb（MZ）（按有效成分计为锰/锌乙撑双二硫代氨基甲酸盐）对两种秀丽隐杆线虫（C. elegans）品系进行慢性（24 小时）或急性（30 分钟）暴露。此外，为了更精确地模拟环境暴露，我们还让线虫先急性暴露于 TD 30 分钟，然后再用不同浓度的 MZ 孵育 30 分钟。我们实验室之前的数据表明，使用 NW1229 线虫（全神经元//绿色荧光蛋白（GFP）构建体）会导致一般性神经元退化。为了确定是否有特定的神经元群体受到优先影响，我们专门使用 EG1285（GABAergic 神经元//GFP 构建体）和 BZ555（DAergic 神经元//GFP 构建体）线虫分别验证 GABAergic 和 DAergic 神经退行性变。结果表明，与对照组（CN）相比，慢性（*P<0.05）和急性（*P<0.05）处理方案中 GABAergic 神经元的绿色像素数量均显著减少。对 BZ555 线虫的分析表明，与 CN 相比，两种处理方案（慢性和急性）中与 DAergic 神经元相关的绿色像素数量均显著减少（*P<0.05）。综上所述，我们的数据表明，TD 和/或 MZ 的暴露会促进模式生物秀丽隐杆线虫中 GABAergic 和 DAergic 神经元的神经退行性变。
