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Methylmercury Exposure and Developmental Neurotoxicity: New Insights from Neural Stem Cells

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Handbook of Neurotoxicity

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Abstract

Methylmercury (MeHg) is a widespread neurotoxic environmental contaminant. The developing nervous system is particularly vulnerable to MeHg toxicity that may have adverse consequences on neurodevelopment depending on the timing and level of exposure. In our daily lives, we can be exposed to MeHg via consumption of contaminated seafood, which is the major MeHg source for humans. While the deleterious effects of exposure to high levels of MeHg are well known and characterized, the consequences and the mechanisms behind the developmental neurotoxic effects induced by low-level exposure are still unclear. Neural stem cells (NSCs) have been proposed as a powerful model to identify the adverse effects on the complex process of nervous system development. This chapter gives an overview of in vitro studies performed in NSCs of different origin with special emphasis on the effects induced by MeHg levels considered to be environmentally relevant to human exposure. Altogether, the data show that MeHg exerts harmful effects at very low concentrations by dysregulating critical neurodevelopmental steps such as proliferation, differentiation, migration, and neurite outgrowth. The use of NSC-based models has made possible the identification of relevant signaling pathways and molecular alterations that point to novel mechanisms of MeHg toxicity.

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Abbreviations

aNSCs:

Adult neural stem cells

CpG:

Cytosine dinucleotide

GD:

Gestational day

GSH:

Glutathione

hiPSC:

Human-induced pluripotent stem cells

hNES:

Human neuroepithelial-like cells

MeHg:

Methylmercury

NSCs:

Neural stem cells

PND:

Postnatal day

ROS:

Reactive oxygen species

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Authors and Affiliations

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

    Raj Bose, Stefan Spulber & Sandra Ceccatelli

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  1. Raj Bose
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  2. Stefan Spulber
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  3. Sandra Ceccatelli
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Correspondence to Raj Bose .

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Editors and Affiliations

  1. Department of Biomedical Sciences, Quillen College of Medicine East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Bose, R., Spulber, S., Ceccatelli, S. (2022). Methylmercury Exposure and Developmental Neurotoxicity: New Insights from Neural Stem Cells. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-031-15080-7_235

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