School of Environmental Engineering, University of Seoul, 163 Siripdaero, Dongdaemun-gu, Seoul 02504, South Korea.
Department of Life Science, University of Seoul, 163 Siripdaero, Dongdaemun-gu, Seoul 02504, South Korea.
Neurotoxicology. 2020 Mar;77:30-39. doi: 10.1016/j.neuro.2019.12.011. Epub 2019 Dec 17.
Graphene oxide (GO) and graphene-based nanomaterials have been widely applied in recent years, but their potential health risk and neurotoxic potentials remain poorly understood. In this study, neurotoxic potential of GO and its underlying molecular and cellular mechanism were investigated using the nematode, Caenorhabditis elegans. Deposition of GO in the head region and increased reactive oxygen species (ROS) was observed in C. elegans after exposure to GO. The neurotoxic potential of GO was then investigated, focusing on neurotransmitters contents and neuronal activity using AFD sensory neurons. The contents of all neurotransmitters, such as, tyrosine, tryptophan, dopamine, tyramine, and GABA, decreased significantly by GO exposure. Decreased fluorescence of Pgcy-8:GFP, a marker of AFD sensory neuron, by GO exposure suggested GO could cause neuronal damage on AFD neuron. GO exposure led decreased expression of ttx-1 and ceh-14, genes required for the function of AFD neurons also confirmed possible detrimental effect of GO to AFD neuron. To understand physiological meaning of AFD neuronal damage by GO exposure, locomotive behavior was then investigated in wild-type as well as in loss-of-function mutants of ttx-1 and ceh-14. GO exposure significantly altered locomotor behavior markers, such as, speed, acceleration, stop time, etc., in wild-type C. elegans, which were mostly rescued in AFD neuron mutants. The present study suggested the GO possesses neurotoxic potential, especially on neurotransmitters and AFD neuron in C. elegans. These findings provide useful information to understand the neurotoxic potential of GO and other graphene-based nanomaterials, which will guide their safe application.
氧化石墨烯（GO）和基于石墨烯的纳米材料近年来得到了广泛应用，但它们的潜在健康风险和神经毒性潜力仍知之甚少。在这项研究中，使用秀丽隐杆线虫（C. elegans）研究了 GO 的神经毒性潜力及其潜在的分子和细胞机制。暴露于 GO 后，在 C. elegans 中观察到 GO 在头部区域的沉积和活性氧物种（ROS）的增加。然后研究了 GO 的神经毒性潜力，重点研究了 AFD 感觉神经元中的神经递质含量和神经元活动。GO 暴露导致所有神经递质的含量，如酪氨酸、色氨酸、多巴胺、酪胺和 GABA，显著降低。GO 暴露导致 Pgcy-8:GFP 的荧光减少，这是 AFD 感觉神经元的标志物，表明 GO 可能对 AFD 神经元造成损伤。GO 暴露导致 ttx-1 和 ceh-14 基因的表达减少，这些基因是 AFD 神经元功能所必需的，这也证实了 GO 对 AFD 神经元可能产生有害影响。为了了解 GO 暴露对 AFD 神经元损伤的生理意义，然后在 ttx-1 和 ceh-14 的野生型和功能缺失突变体中研究了运动行为。GO 暴露显著改变了野生型 C. elegans 的运动行为标志物，如速度、加速度、停止时间等，这些标志物在 AFD 神经元突变体中大多得到了挽救。本研究表明，GO 具有神经毒性潜力，特别是对 C. elegans 中的神经递质和 AFD 神经元。这些发现为理解 GO 和其他基于石墨烯的纳米材料的神经毒性潜力提供了有用的信息，这将指导它们的安全应用。
