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Caenorhabditis elegans as a Predictive Model for Methylmercury-Induced Neurotoxicity

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Methylmercury and Neurotoxicity

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 2))

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Abstract

Several targets and detoxifying components of methylmercury (MeHg) toxicity, including glutathione (GSH), metallothioneins (MTs), and heat shock proteins (HSPs), have been identified to date. In our most recent studies, we have used the model organism, Caenorhabditis elegans, to examine many of the unknown molecular mechanisms of MeHg neurotoxicity. While MeHg accumulated within C. elegans was shown to cause a delay in development as well as a decreased pharyngeal pumping rate, many endpoints, including nervous system morphology, were unaffected. These findings led to the hypothesis that C. elegans has unique mechanisms for protecting its nervous system from MeHg neurotoxicity. Therefore, we examined the involvement of GSH, MTs, and HSPs in MeHg toxicity in C. elegans. We found that GSH levels were altered upon MeHg exposure, a glutathione s-transferase was highly upregulated upon exposure, and the lack of MTs resulted in increased sensitivity to the toxicant. We also demonstrated that MeHg induces hormesis in C. elegans, which is most likely due, at least in part, to the involvement of glutathione transferases in MeHg toxicity. The molecular mechanisms of MeHg neuroprotection in C. elegans, which we identify in this review, may prove valuable in developing effective strategies to protect human health.

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Abbreviations

C. elegans :

Caenorhabditis elegans

CGC:

Caenorhabditis genetics center

Cys:

Cysteine

GFP:

Green fluorescent protein

GSH:

Glutathione

GSSG:

Oxidized glutathione

GST:

Glutathione transferase

gst-4:

Glutathione S-transferase 4

Hg:

Mercury

hsp-16 :

Heat shock protein 16

hsp-4 :

Heat shock protein 4

HSPs:

Heat shock proteins

LD50:

Lethal dose 50

MeHg:

Methylmercury

MT:

Metallothionein

mtl-1 :

Metallothionein 1

mtl-2 :

Metallothionein 2

RNAi:

RNA interference

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Acknowledgments

This work was supported by a training grant from the NIEHS T32 ES007028 to KJH and NIEHS R01 07331 to MA.

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Authors and Affiliations

  1. Nicholas School of the Environment, Duke University, Durham, NC, USA

    Kirsten J. Helmcke

  2. Department of Pediatrics and Pharmacology, and the Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, 2215-B Garland Avenue, 11415 MRB IV, Nashville, TN, 37232-0414, USA

    Michael Aschner PhD

Authors
  1. Kirsten J. Helmcke
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  2. Michael Aschner PhD
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Corresponding author

Correspondence to Michael Aschner PhD .

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Editors and Affiliations

  1. , Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden

    Sandra Ceccatelli

  2. , Department of Pediatrics, Vanderbilt University Medical Center, Garland Avenue 2215-B, Nashville, 37232, Tennessee, USA

    Michael Aschner

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Helmcke, K.J., Aschner, M. (2012). Caenorhabditis elegans as a Predictive Model for Methylmercury-Induced Neurotoxicity. In: Ceccatelli, S., Aschner, M. (eds) Methylmercury and Neurotoxicity. Current Topics in Neurotoxicity, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2383-6_18

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