4.7 Article

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

期刊

TOXICOLOGY
卷 411, 期 -, 页码 154-162

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2018.10.006

关键词

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

资金

  1. CNPq [202896/2014-5]
  2. Federal University of Santa Maria
  3. National Institute of Environmental Health Sciences [NIEHS R01ES07331, NIEHS R01ES10563, NIEHS R01ES020852]
  4. NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES007331, R01ES010563] Funding Source: NIH RePORTER

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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 Ll 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 mu M 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 mu M 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.

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