Quinolinic acid and glutamatergic neurodegeneration in Caenorhabditis elegans

Tássia Limana da Silveira, Daniele Coradine Zamberlan, Leticia Priscilla Arantes, Marina Lopes Machado, Thayanara Cruz da Silva, Daniela de Freitas Câmara, Abel Santamaría, Michael Aschner, Felix Alexandre Antunes Soares

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)94-101
Number of pages8
JournalNeurotoxicology
Volume67
DOIs
StatePublished - Jul 2018

Keywords

  • C. elegans
  • Glutamatergic system
  • NMDA
  • Neurodegeneration
  • Quinolinic acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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    da Silveira, T. L., Zamberlan, D. C., Arantes, L. P., Machado, M. L., da Silva, T. C., Câmara, D. D. F., Santamaría, A., Aschner, M., & Soares, F. A. A. (2018). Quinolinic acid and glutamatergic neurodegeneration in Caenorhabditis elegans. Neurotoxicology, 67, 94-101. https://doi.org/10.1016/j.neuro.2018.04.015