NanoSafety Group, International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal.
NanoSafety Group, International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal.
Environ Int. 2024 Apr;186:108597. doi: 10.1016/j.envint.2024.108597. Epub 2024 Mar 22.
The growing body of evidence links exposure to particulate matter pollutants with an increased risk of neurodegenerative diseases. In the present study, we investigated whether diesel exhaust particles can induce neurobehavioral alterations associated with neurodegenerative effects on glutamatergic and dopaminergic neurons in Caenorhabditis elegans (C. elegans). Exposure to DEP at concentrations of 0.167 µg/cm and 1.67 µg/cm resulted in significant developmental delays and altered locomotion behaviour. These effects were accompanied by discernible alterations in the expressions of antioxidant genes sod-3 and gst-4 observed in transgenic strains. Behaviour analysis demonstrated a significant reduction in average speed (p < 0.001), altered paths, and decreased swimming activities (p < 0.01), particularly at mid and high doses. Subsequent assessment of neurodegeneration markers in glutamatergic (DA1240) and dopaminergic (BZ555) transgenic worms revealed notable glutamatergic neuron degeneration at 0.167 μg/cm (∼30 % moderate, ∼20 % advanced) and 1.67 μg/cm (∼28 % moderate, ∼24 % advanced, p < 0.0001), while dopaminergic neurons exhibited structural deformities (∼16 %) without significant degeneration in terms of blebs and breaks. Furthermore, in silico docking simulations suggest the presence of an antagonistic competitive inhibition induced by DEP in the evaluated neuro-targets, stronger for the glutamatergic transporter than for the dopaminergic receptor from the comparative binding affinity point of view. The results underscore DEP's distinctive neurodegenerative effects and suggest a link between locomotion defects and glutamatergic neurodegeneration in C. elegans, providing insights into environmental health risks assessment.
越来越多的证据表明，暴露于颗粒物污染物与神经退行性疾病的风险增加有关。在本研究中，我们研究了柴油机排气颗粒是否会引起与神经退行性作用相关的神经行为改变，这些作用会影响秀丽隐杆线虫（C. elegans）中的谷氨酸能和多巴胺能神经元。暴露于 DEP 的浓度为 0.167µg/cm 和 1.67µg/cm 会导致明显的发育延迟和运动行为改变。这些影响伴随着在转基因株系中观察到的抗氧化基因 sod-3 和 gst-4 的表达发生明显改变。行为分析表明，平均速度显著降低（p<0.001），路径改变，游泳活动减少（p<0.01），尤其是在中高剂量时。随后对谷氨酸能（DA1240）和多巴胺能（BZ555）转基因蠕虫的神经退行性标志物进行评估，结果表明，在 0.167µg/cm（约 30%中度，约 20%晚期）和 1.67µg/cm（约 28%中度，约 24%晚期，p<0.0001）时，明显的谷氨酸能神经元退化，而多巴胺能神经元表现出结构畸形（约 16%），但在泡囊和断裂方面没有明显退化。此外，基于计算机的对接模拟表明，DEP 在评估的神经靶标中引起了拮抗竞争抑制，从比较结合亲和力的角度来看，对谷氨酸转运体的抑制作用强于对多巴胺受体的抑制作用。研究结果强调了 DEP 的独特神经退行性作用，并表明秀丽隐杆线虫运动缺陷与谷氨酸能神经退行性之间存在联系，为环境健康风险评估提供了新的见解。
