Le Dang Tri, Pauls Stella, Poschmann Gereon, Stühler Kai, von Mikecz Anna
Leibniz Research Institute of Environmental Medicine GmbH (IUF), Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Cells. 2025 Jan 27;14(3):190. doi: 10.3390/cells14030190.
Although is commonly used to assess the neurotoxicity of environmental pollutants, studies that explore the intricate biology of its nervous system, particularly those addressing long-term effects and aging in adult worms, are rare. These models offer significant advantages for understanding the full spectrum of neurobiological impacts. Here, we investigated the effects of silica nanomaterials on the γ-aminobutyric acid (GABA) neural system in young to middle-aged nematodes and found a unique degeneration pattern characterized by loss of anterior- and posteriormost GABAergic D-type motor neurons. Four-day-old nematodes were identified as a vulnerable age group, where the pollutant-accelerated neurodegeneration that is typically seen in old . Proteomics of 4-day-old revealed significant alterations of protein abundance, including the downregulation of proteins such as glutamate dehydrogenase (gdh-1) and glutamate oxaloacetate transaminase (got-1.2), which are essentially involved in GABA metabolic pathways. Consistent with these findings, we demonstrated locomotion deficits in exposed to nanoscale silica by establishing a semi-automated behavioral arena. Our setup not only visualizes but also automatically quantifies vulnerabilities at the individual worm level. This novel neurodegeneration model now enables the simulation of real-world pollutant mixtures and environmental conditions, capturing the complexity of the exposome.
尽管 常用于评估环境污染物的神经毒性，但探索其神经系统复杂生物学的研究却很少，尤其是那些针对成年蠕虫长期影响和衰老的研究。这些模型为理解神经生物学影响的全貌提供了显著优势。在这里，我们研究了二氧化硅纳米材料对年轻至中年线虫γ-氨基丁酸（GABA）神经系统的影响，发现了一种独特的退化模式，其特征是最前和最后端的GABA能D型运动神经元缺失。4日龄的线虫被确定为一个脆弱的年龄组，在这个年龄组中，污染物加速的神经退行性变通常出现在老年 中。对4日龄 的蛋白质组学分析显示蛋白质丰度有显著变化，包括谷氨酸脱氢酶（gdh-1）和谷氨酸草酰乙酸转氨酶（got-1.2）等蛋白质的下调，这些蛋白质主要参与GABA代谢途径。与这些发现一致，我们通过建立一个半自动行为实验场证明了暴露于纳米级二氧化硅的 存在运动缺陷。我们的装置不仅可以可视化，还可以在个体蠕虫水平上自动量化脆弱性。这个新的神经退行性变模型现在能够模拟现实世界中的污染物混合物和环境条件，捕捉暴露组的复杂性。
