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Redox State in Mediating Methylmercury Neurotoxicity

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Methylmercury and Neurotoxicity

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

Abstract

Methylmercury (MeHg) is an environmental pollutant that has been reported to induce neurotoxicity in both animals and humans. Although the molecular mechanisms underlying MeHg toxicity remain elusive, several lines of evidence indicate that MeHg is able to change the redox state of particular redox couples (i.e., reduced/oxidized glutathione (GSH), reduced/oxidized sulfhydryl or selenohydryl proteins, etc.), thus changing the entire cellular redox environment. These events contribute to oxidative stress, which culminates in neurotoxicity. Although MeHg-induced changes in the redox state are related to its direct interactions with nucleophilic molecules, such as GSH or sulfhydryl/selenohydryl proteins, it is noteworthy that MeHg can cause neurotoxicity even when present in concentrations 100- to 1,000-fold less than those of these nucleophiles. Accordingly, recent evidence indicates that specific nucleophilic molecules (not yet fully identified) are primarily and/or preferentially targeted by MeHg due to their particular high reactivity toward this toxicant, thus initiating a cascade of molecular events that culminate in neurotoxicity.

In this chapter, we give an initial background on the general concepts regarding the redox state and its important role in counteracting oxidative stress in the central nervous system, followed by discussions on the potential interaction of MeHg with redox couplers (mainly nucleophilic thiol- and selenol-containing molecules). Taking into account that the knowledge concerning such molecules (“primary MeHg neurotargets”) and their involvement in MeHg-induced neurotoxicity is not yet completely understood, further research in this area is well warranted.

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Acknowledgments

The author would like to thank the colleagues/coauthors who have contributed to several studies referenced in this chapter. These studies were funded in part by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and from the National Institute of Environmental Health Sciences.

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Authors and Affiliations

  1. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Marcelo Farina

  2. Departments 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

  3. Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    João B. T. Rocha

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Correspondence to Michael Aschner PhD .

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  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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Farina, M., Aschner, M., Rocha, J.B.T. (2012). Redox State in Mediating Methylmercury 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_6

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