McVey Kenneth A, Snapp Isaac B, Johnson Megan B, Negga Rekek, Pressley Aireal S, Fitsanakis Vanessa A
King University, Department of Biology, 1350 King College Road, Bristol, TN 37620, USA; Liberty University College of Osteopathic Medicine, 306 Liberty View Lane, Lynchburg, VA 24502, USA.
King University, Department of Biology, 1350 King College Road, Bristol, TN 37620, USA; Medical University of South Carolina, Physician Assistant Studies, 151B Rutledge Avenue, Charleston, SC 29425, USA.
Neurotoxicol Teratol. 2016 May-Jun;55:23-31. doi: 10.1016/j.ntt.2016.03.002. Epub 2016 Mar 26.
Recent data demonstrate that chronic exposure of Caenorhabditis elegans (C. elegans) to a high-use glyphosate-containing herbicide, Touchdown (TD), potentially damages the adult nervous system. It is unknown, however, whether unhatched worms exposed to TD during the egg stage show abnormal neurodevelopment post-hatching. Therefore, we investigated whether early treatment with TD leads to aberrant neuronal or neurite development in C. elegans. Studies were completed in three different worm strains with green fluorescent protein (GFP)-tagged neurons to facilitate visual neuronal assessment. Initially, eggs from C. elegans with all neurons tagged with GFP were chronically exposed to TD. Visual inspection suggested decreased neurite projections associated with ventral nerve cord neurons. Data analysis showed a statistically significant decrease in overall green pixel numbers at the fourth larval (L4) stage (*p<0.05). We further investigated whether specific neuronal populations were preferentially vulnerable to TD by treating eggs from worms that had all dopaminergic (DAergic) or γ-aminobutyric acid (GABAergic) neurons tagged with GFP. As before, green pixel number associated with these discrete neuronal populations was analyzed at multiple larval stages. Data analysis indicated statistically significant decreases in pixel number associated with DAergic, but not GABAergic, neurons (***p<0.001) at all larval stages. Finally, statistically significant decreases (at the first larval stage, L1) or increases (at the fourth larval stage, L4) in superoxide levels, a developmental signaling molecule, were detected (*p<0.05). These data suggest that early exposure to TD may impair neuronal development, perhaps through superoxide perturbation. Since toxic insults during development may late render individuals more vulnerable to neurodegenerative diseases in adulthood, these studies provide some of the first evidence in this model organism that early exposure to TD may adversely affect the developing nervous system.
近期数据表明，秀丽隐杆线虫（简称线虫）长期接触高用量含草甘膦除草剂“通达”（TD）可能会损害成虫的神经系统。然而，尚不清楚在卵期接触TD的未孵化线虫在孵化后是否会出现神经发育异常。因此，我们研究了TD早期处理是否会导致线虫神经元或神经突发育异常。我们使用三种不同的带有绿色荧光蛋白（GFP）标记神经元的线虫品系完成了研究，以方便进行视觉神经元评估。最初，将所有神经元都标记有GFP的线虫的卵长期暴露于TD中。视觉检查显示腹侧神经索神经元的神经突投射减少。数据分析表明，在第四幼虫（L4）阶段，总体绿色像素数量有统计学意义的下降（*p<0.05）。我们进一步研究了特定神经元群体是否更容易受到TD的影响，方法是处理所有多巴胺能（DAergic）或γ-氨基丁酸能（GABAergic）神经元都标记有GFP的线虫的卵。和之前一样，在多个幼虫阶段分析与这些离散神经元群体相关的绿色像素数量。数据分析表明，在所有幼虫阶段，与DAergic神经元相关的像素数量有统计学意义的下降（***p<0.001），而与GABAergic神经元相关的像素数量没有下降。最后，检测到发育信号分子超氧化物水平在第一幼虫阶段（L1）有统计学意义的下降，在第四幼虫阶段（L4）有统计学意义的上升（*p<0.05）。这些数据表明，早期接触TD可能会损害神经元发育，可能是通过超氧化物扰动。由于发育过程中的毒性损伤可能会使个体在成年后更容易患神经退行性疾病，这些研究在这种模式生物中首次提供了一些证据，表明早期接触TD可能会对发育中的神经系统产生不利影响。
