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

• Published in: Toxicology (Amsterdam) Vol. 411; pp. 154 - 162
• Main Authors: Schetinger, Maria Rosa Chitolina, Peres, Tanara V., Arantes, Letícia P., Carvalho, Fabiano, Dressler, Valderi, Heidrich, Graciela, Bowman, Aaron B., Aschner, Michael
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-01-2019
• Subjects: Animals; Behavioral tasks; Biogenic Monoamines - biosynthesis; C. elegans; Caenorhabditis elegans; Caenorhabditis elegans Proteins - biosynthesis; Caenorhabditis elegans Proteins - genetics; Development; Female; Larva - drug effects; Lethal Dose 50; Male; Manganese - pharmacokinetics; Manganese - toxicity; Metal interaction; Methylmercury Compounds - pharmacokinetics; Methylmercury Compounds - toxicity; Movement Disorders; Nerve Degeneration - chemically induced; Nerve Degeneration - pathology; Neurodegeneration; Oxidative Stress - drug effects; Parasympathetic Nervous System - drug effects; Reproduction; Up-Regulation - drug effects; Behavioral tasks; Development; Metal interaction; C. elegans; Neurodegeneration
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2018.10.006

Overview of all the results obtained in this work. MeHg (methylmercury), Mn (manganese), LD50 (lethal dose that kills 50% of the animals), ace-2 (acetylcholinesterase-2), cat-1 (Vesicular monoamine transporter/VMAT), sod-3 (superoxide dismutase-3), sod-4 (superoxide dismutase-4), ctl-3 (catalase-1), LX929 (fluorescent strain to cholinergic neurons).
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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.