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Heavy metals, behavior, and neurodegeneration: using Caenorhabditis elegans to untangle a can of worms

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Metal Ions in Neurological Systems

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Abstract

The complexity of the vertebrate brain has made the study of neurodegenerative disease processes slow, difficult, and expensive. Caenorhabditis elegans offers viable in vivo model system for addressing numerous issues pertinent to neurodegenerative diseases. Differentiation and migration patterns in the nematode are well characterized, thus allowing for analysis of changes in nervous system in response to mutations and toxic insults. The full sequencing of the nematode genome and a high-density map of polymorphisms for the wild type nematode allows for mapping of gene mutations and linking of mechanisms of neurodegeneration to genetic susceptibility. In addition to the high level of gene conservation, the processes of synaptic release, trafficking and formation are also conserved between this invertebrate and mammalians. Given these advantages, C. elegans has been employed in numerous studies to address neurodegeneration and mechanisms of toxicity of a wide range of toxicants. In this chapter, we provide an overview on the system model and discuss contemporary insights derived from C. elegans on the involvement of metals in behavior and neurodegenerative diseases.

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Abbreviations

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

DA:

Dopamine

DAergic:

Dopaminergic

DMT1:

Divalent metal transporter 1

GABA:

γ-aminobutyric acid

GST:

Glutathione-S-transferase

LRRK2:

Leucine-rich repeat kinase 2

MeHg:

Methylmercury

MPT:

Mitochondrial permeability transition

NGM:

Nematode growth medium

Nrf2:

Nuclear factor-2 erythroid 2-related factor-2

PD:

Parkinson’s disease

PHP:

Psuedohyperphosphorylated

PINK1:

PTEN-induced novel kinase 1

PTEN:

Phosphatase and tensin homolog

ROS:

Reactive oxygen species

SNpc:

Substantia nigra pars compacta

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Acknowledgments

We are grateful for support by NIEHS R01ES07331, R01ES10563, the Center in Molecular Toxicology NIH grant P30ES00267, and the training program in Environmental Toxicology grant T32ES007028.

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Authors and Affiliations

  1. Division of Clinical Pharmacology and Pediatric Toxicology, Vanderbilt University Medical Center, Nashville, TN, USA

    Samuel Caito

  2. Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, TN, USA

    Samuel Caito & Michael Aschner

  3. Division of Clinical Pharmacology and Pediatric Toxicology, Vanderbilt University Medical Center, 11425 MRB IV 2215-B Garland Avenue, Nashville, TN, 37232-0414, USA

    Michael Aschner

  4. Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN, USA

    Michael Aschner

  5. The Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, TN, USA

    Michael Aschner

Authors
  1. Samuel Caito
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  2. Michael Aschner
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Correspondence to Michael Aschner .

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Editors and Affiliations

  1. , Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9, Vienna, 1060, Austria

    Wolfgang Linert

  2. Faculty of Chemistry, University of Wroclaw, ul. Fryderyka Joliot Curie 14, Wroclaw, 50-383, Poland

    Henryk Kozlowski

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© 2012 Springer-Verlag Wien

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Caito, S., Aschner, M. (2012). Heavy metals, behavior, and neurodegeneration: using Caenorhabditis elegans to untangle a can of worms. In: Linert, W., Kozlowski, H. (eds) Metal Ions in Neurological Systems. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1001-0_15

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