The 2,3-Pyridinedicarboxylic acid, widely known as quinolinic acid (QA), is a metabolite of tryptophan degradation in kynurenine pathway, which acts as a NMDA receptor agonist. Within the brain, QA is produced only by microglia and activated macrophages. Furthermore, QA has been described as a potent endogenous neurotoxin, when present at high levels, related to various psychiatric disorders and neurodegenerative processes. The nematode Caenorhabditis elegans has a nervous system highly conserved with mammals and thus is an alternative animal model widely used in neurobiology research. However, there is no neurotoxin described that allows the study of glutamatergic system disturbance in C. elegans. The aim of this study was verify if QA can induce neurotoxicity in C. elegans, due to its action in glutamatergic system. Nematodes from N2 (wild type) and transgenic strains VM487 (
nmr-1), VC2623 (
nmr-2), TJ356(
daf-16::GFP), CL2070 (
hsp-16,2::GFP), CL2166 (
gst-4::GFP) and CF1553 (
sod-3::GFP) at young adult stage were treated in liquid or agar containing QA in different concentrations (5, 10, 20, 50, 100 and 200 mM) or vehicle (M9 buffer) at 20oC for 1 hour. The analyses included evaluation of QA's effects on survival, behavioral parameters (pharynx pumping and locomotion), subcellular DAF-16 localization, reactive species generation and expression of superoxide dismutase 3, glutathione-S-transferase-4, and heat shock protein 16.2. When used at high concentrations (50, 100 and 200 mM) QA can induced and increase in C elegans mortality (~15%), although when used at low concentrations (10 and 20mM) QA altered some behavioral pattern of the nematodes. The QA can leave to an increase in the expression of
hsp-16.2 (~15%) as well as
gst-4 (~40%). However,
sod-3 levels were not significantly different from control group. QA also activated DAF-16/FOXO signaling pathway and increased reactive species levels compared to control group. When used specific strains of glutamatergic system, the increase in reactive species production occur in a
nmr-1-dependent manner. Our data suggests that QA might be used for neurotoxicological studies on glutamatergic system injuries associated with oxidative stress in C. elegans.