PMID- 29702159 OWN - NLM STAT- MEDLINE DCOM- 20190408 LR - 20190701 IS - 1872-9711 (Electronic) IS - 0161-813X (Print) IS - 0161-813X (Linking) VI - 67 DP - 2018 Jul TI - Quinolinic acid and glutamatergic neurodegeneration in Caenorhabditis elegans. PG - 94-101 LID - S0161-813X(18)30127-X [pii] LID - 10.1016/j.neuro.2018.04.015 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - da Silveira, Tassia Limana AU - da Silveira TL AD - Universidade Federal de Santa Maria, Centro de Ciencias Naturais e Exatas, Departamento de Bioquimica e Biologia Molecular, Programa de Pos-graduacao em Ciencias Biologicas: Bioquimica Toxicologica, Camobi, 97105-900, Santa Maria, RS, Brazil. FAU - Zamberlan, Daniele Coradine AU - Zamberlan DC AD - Universidade Federal de Santa Maria, Centro de Ciencias Naturais e Exatas, Departamento de Bioquimica e Biologia Molecular, Programa de Pos-graduacao em Ciencias Biologicas: Bioquimica Toxicologica, Camobi, 97105-900, Santa Maria, RS, Brazil. FAU - Arantes, Leticia Priscilla AU - Arantes LP AD - Universidade Federal de Santa Maria, Centro de Ciencias Naturais e Exatas, Departamento de Bioquimica e Biologia Molecular, Programa de Pos-graduacao em Ciencias Biologicas: Bioquimica Toxicologica, Camobi, 97105-900, Santa Maria, RS, Brazil. FAU - Machado, Marina Lopes AU - Machado ML AD - Universidade Federal de Santa Maria, Centro de Ciencias Naturais e Exatas, Departamento de Bioquimica e Biologia Molecular, Programa de Pos-graduacao em Ciencias Biologicas: Bioquimica Toxicologica, Camobi, 97105-900, Santa Maria, RS, Brazil. FAU - da Silva, Thayanara Cruz AU - da Silva TC AD - Universidade Federal de Santa Maria, Centro de Ciencias Naturais e Exatas, Departamento de Bioquimica e Biologia Molecular, Programa de Pos-graduacao em Ciencias Biologicas: Bioquimica Toxicologica, Camobi, 97105-900, Santa Maria, RS, Brazil. FAU - Camara, Daniela de Freitas AU - Camara DF AD - Universidade Federal de Santa Maria, Centro de Ciencias Naturais e Exatas, Departamento de Bioquimica e Biologia Molecular, Programa de Pos-graduacao em Ciencias Biologicas: Bioquimica Toxicologica, Camobi, 97105-900, Santa Maria, RS, Brazil. FAU - Santamaria, Abel AU - Santamaria A AD - Laboratorio de Aminoacidos Excitadores, Instituto Nacional de Neurologia y Neurocirugia, Insurgentes Sur 3877, 14269 Ciudad de Mexico, Mexico. FAU - Aschner, Michael AU - Aschner M AD - Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, NY 10461, USA. FAU - Soares, Felix Alexandre Antunes AU - Soares FAA AD - Universidade Federal de Santa Maria, Centro de Ciencias Naturais e Exatas, Departamento de Bioquimica e Biologia Molecular, Programa de Pos-graduacao em Ciencias Biologicas: Bioquimica Toxicologica, Camobi, 97105-900, Santa Maria, RS, Brazil. Electronic address: felix@ufsm.br. LA - eng GR - R21 ES025415/ES/NIEHS NIH HHS/United States GR - T32 ES007331/ES/NIEHS NIH HHS/United States GR - R03 ES024849/ES/NIEHS NIH HHS/United States GR - R01 ES007331/ES/NIEHS NIH HHS/United States GR - R01 ES010563/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180424 PL - Netherlands TA - Neurotoxicology JT - Neurotoxicology JID - 7905589 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Reactive Oxygen Species) RN - 3KX376GY7L (Glutamic Acid) RN - F6F0HK1URN (Quinolinic Acid) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Caenorhabditis elegans MH - Caenorhabditis elegans Proteins/*metabolism MH - Dose-Response Relationship, Drug MH - Glutamic Acid/*metabolism MH - Locomotion/drug effects/physiology MH - Neurodegenerative Diseases/*chemically induced/*metabolism MH - Quinolinic Acid/*toxicity MH - Reactive Oxygen Species/metabolism MH - Touch/drug effects/physiology PMC - PMC6054819 MID - NIHMS964880 OTO - NOTNLM OT - C. elegans OT - Glutamatergic system OT - NMDA OT - Neurodegeneration OT - Quinolinic acid COIS- Conflict of Interest The authors declare that they have no conflict of interest. EDAT- 2018/04/28 06:00 MHDA- 2019/04/09 06:00 PMCR- 2019/07/01 CRDT- 2018/04/28 06:00 PHST- 2017/10/12 00:00 [received] PHST- 2018/02/15 00:00 [revised] PHST- 2018/04/16 00:00 [accepted] PHST- 2018/04/28 06:00 [pubmed] PHST- 2019/04/09 06:00 [medline] PHST- 2018/04/28 06:00 [entrez] PHST- 2019/07/01 00:00 [pmc-release] AID - S0161-813X(18)30127-X [pii] AID - 10.1016/j.neuro.2018.04.015 [doi] PST - ppublish SO - Neurotoxicology. 2018 Jul;67:94-101. doi: 10.1016/j.neuro.2018.04.015. Epub 2018 Apr 24.