Quinolinic acid (QUIN) is an endogenous neurotoxin that acts as an N-methyl-D-aspartate receptor (NMDAR) agonist generating a toxic cascade, which can lead to neurodegeneration. The action of QUIN in Caenorhabditis elegans and the neurotoxins that allow the study of glutamatergic system disorders have not been carefully addressed. The effects of QUIN on toxicological and behavioral parameters in VM487 and VC2623 transgenic, as well as wild-type (WT) animals were performed to evaluate whether QUIN could be used as a neurotoxin in C. elegans. QUIN reduced survival of WT worms in a dose-dependent manner. A sublethal dose of QUIN (20 mM) increased reactive oxygen species (ROS) levels in an nmr-1/NMDAR-dependent manner, activated the DAF-16/FOXO transcription factor, and increased expression of the antioxidant enzymes, superoxide dismutase-3, glutathione S-transferase-4, and heat shock protein-16.2. QUIN did not change motor behavioral parameters, but altered the sensory behavior in N2 and VM487 worms. Notably, the effect of QUIN on the sensory behavioral parameters might occur, at least in part, secondary to increased ROS. However, the touch response behavior indicates a mechanism of action that is independent of ROS generation. In addition, non-lethal doses of QUIN triggered neurodegeneration in glutamatergic neurons. Our findings indicate that C. elegans might be useful as a model for studies of QUIN as a glutamatergic neurotoxin in rodent models.

喹啉酸（QUIN）是一种内源性神经毒素，可作为N-甲基-D-天冬氨酸受体（NMDAR）激动剂，产生有毒级联反应，可导致神经退行性变。QUIN在秀丽隐杆线虫和允许研究谷氨酸能系统疾病的神经毒素中的作用尚未得到仔细研究。进行QUIN对VM487和VC2623转基因动物以及野生型（WT）动物的毒理学和行为参数的影响，以评估QUIN是否可以用作秀丽隐杆线虫的神经毒素。QUIN以剂量依赖性方式降低了WT蠕虫的存活率。亚致死剂量QUIN（20 mM）增加了nmr-1中的活性氧（ROS）水平/ NMDAR依赖性方式，激活DAF-16 / FOXO转录因子，并增加抗氧化酶，超氧化物歧化酶3，谷胱甘肽S-转移酶4和热休克蛋白16.2的表达。QUIN并没有改变运动行为参数，但是改变了N2和VM487蠕虫的感觉行为。值得注意的是，QUIN对感觉行为参数的影响可能至少部分是继ROS增加之后发生的。但是，触摸响应行为表示一种独立于ROS生成的作用机制。此外，非致死剂量的QUIN触发了谷氨酸能神经元的神经变性。我们的发现表明，秀丽隐杆线虫可能可用作研究QUIN作为啮齿动物模型中的谷氨酸能神经毒素的模型。