Combined exposure to methylmercury and manganese during L1 larval stage causes motor dysfunction, cholinergic and monoaminergic up-regulation and oxidative stress in L4 Caenorhabditis elegans

Maria Rosa Chitolina Schetinger, Tanara V. Peres, Letícia P. Arantes, Fabiano Carvalho, Valderi Dressler, Graciela Heidrich, Aaron B. Bowman, Michael Aschner

Research output: Contribution to journalArticle

Abstract

Humans are exposed simultaneously to a variety of neurotoxic agents, including manganese (Mn) and methylmercury (MeHg). Therefore, the study of combined exposures to toxicants is timely. This work aimed to study changes in cholinergic system focusing on acetylcholinesterase (ace-2), monoaminergic system focusing on vesicular monoamine transporter (VMAT, cat-1) expression, to address changes in antioxidant enzymatic systems, namely, the expression of superoxide dismutase (sod-3 and sod-4) and catalase (ctl-3), as well as worm reproduction and locomotion. C. elegans in the L1 larval stage were exposed to Mn, MeHg or both. All analyses were done 24 h after the end of exposure, except for behavior and reproduction tests that were assessed in L4 larval stage worms. The values obtained for lethal dose 50% (LD50) were 17.78 mM for Mn and 30.63 μM for MeHg. It was observed that body bends, pharyngeal pumping and brood size decreased in worms exposed to metals when undergoing combined exposures. Relative mRNA content of ace-2, cat-1, sod-3, sod-4 and ctl-3 was increased at the highest concentration of the interaction (50 mM Mn + 50 μM MeHg). Cholinergic degeneration was observed in all groups co-exposed to both metals. Notably, combined exposure to metals was more toxic to the worms than when exposed to a single metal.

Original languageEnglish (US)
JournalToxicology
DOIs
StateAccepted/In press - Jan 1 2018

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Oxidative stress
Caenorhabditis elegans
Manganese
Cholinergic Agents
Oxidative Stress
Up-Regulation
Metals
Reproduction
Cats
Vesicular Monoamine Transport Proteins
Poisons
Lethal Dose 50
Locomotion
Acetylcholinesterase
Catalase
Superoxide Dismutase
Antioxidants
Messenger RNA

Keywords

  • Behavioral tasks
  • C. elegans
  • Development
  • Metal interaction
  • Neurodegeneration

ASJC Scopus subject areas

  • Toxicology

Cite this

Combined exposure to methylmercury and manganese during L1 larval stage causes motor dysfunction, cholinergic and monoaminergic up-regulation and oxidative stress in L4 Caenorhabditis elegans. / Schetinger, Maria Rosa Chitolina; Peres, Tanara V.; Arantes, Letícia P.; Carvalho, Fabiano; Dressler, Valderi; Heidrich, Graciela; Bowman, Aaron B.; Aschner, Michael.

In: Toxicology, 01.01.2018.

Research output: Contribution to journalArticle

Schetinger, Maria Rosa Chitolina ; Peres, Tanara V. ; Arantes, Letícia P. ; Carvalho, Fabiano ; Dressler, Valderi ; Heidrich, Graciela ; Bowman, Aaron B. ; Aschner, Michael. / Combined exposure to methylmercury and manganese during L1 larval stage causes motor dysfunction, cholinergic and monoaminergic up-regulation and oxidative stress in L4 Caenorhabditis elegans. In: Toxicology. 2018.
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