Skip Navigation

Publication Detail

Title: Caenorhabditis elegans as a model for studies on quinolinic acid-induced NMDAR-dependent glutamatergic disorders.

Authors: Limana da Silveira, Tássia; Lopes Machado, Marina; Bicca Obetine Baptista, Fabiane; Farina Gonçalves, Débora; Duarte Hartmann, Diane; Marafiga Cordeiro, Larissa; Franzen da Silva, Aline; Lenz Dalla Corte, Cristiane; Aschner, Michael; Antunes Soares, Felix Alexandre

Published In Brain Res Bull, (2021 10)

Abstract: Quinolinic acid (QUIN) is an agonist of the neurotransmitter glutamate (Glu) capable of binding to N-methyl-D-aspartate receptors (NMDAR) increasing glutamatergic signaling. QUIN is known for being an endogenous neurotoxin, able to induce neurodegeneration. In Caenorhabditis elegans, the mechanism by which QUIN induces behavioral and metabolic toxicity has not been fully elucidated. The effects of QUIN on behavioral and metabolic parameters in nmr-1 and nmr-2 NMDA receptors in transgenic and wild-type (WT) worms were performed to decipher the pathway by which QUIN exerts its toxicity. QUIN increased locomotion parameters such as wavelength and movement amplitude medium, as well as speed and displacement, without modifying the number of body bends in an NMDAR-dependent-manner. QUIN increased the response time to the chemical stimulant 1-octanol, which is modulated by glutamatergic neurotransmission in the ASH neuron. Brood size increased after exposure to QUIN, dependent upon nmr-2/NMDA-receptor, with no change in lifespan. Oxygen consumption, mitochondrial membrane potential, and the flow of coupled and unbound electrons to ATP production were reduced by QUIN in wild-type animals, but did not alter citrate synthase activity, altering the functionality but the mitochondrial viability. Notably, QUIN modified fine locomotor and chemosensory behavioral parameters, as well as metabolic parameters, analogous to previously reported effects in mammals. Our results indicate that QUIN can be used as a neurotoxin to elicit glutamatergic dysfunction in C. elegans in a way analogous to other animal models.

PubMed ID: 34271120 Exiting the NIEHS site

MeSH Terms: 1-Octanol/pharmacology; Adenosine Triphosphate/biosynthesis; Amino Acid Metabolism, Inborn Errors/chemically induced*; Animals; Animals, Genetically Modified; Caenorhabditis elegans/physiology*; Citrate (si)-Synthase/metabolism; Disease Models, Animal; Glutamic Acid/metabolism; Humans; Kynurenine/metabolism; Motor Activity/drug effects; Neurodegenerative Diseases/chemically induced; Neurodegenerative Diseases/genetics; Quinolinic Acid*; Receptors, N-Methyl-D-Aspartate/drug effects*; Receptors, N-Methyl-D-Aspartate/genetics*; Signal Transduction/drug effects; Synaptic Transmission

Back
to Top
Last Reviewed: October 02, 2024