PUBLICATION

Gene-Environment Interactions: Neurodegeneration in Non-Mammals and Mammals

Authors
Aschner, M., Levin, E.D., Suñol, C., Olopade, J.O., Helmcke, K.J., Avila, D.S., Sledge, D., Ali, R.H., Upchurch, L., Donerly, S., Linney, E., Forsby, A., Ponnoru, P., and Connor, J.R.
ID
ZDB-PUB-100408-12
Date
2010
Source
Neurotoxicology   31(5): 582-588 (Review)
Registered Authors
Donerly, Sue, Linney, Elwood
Keywords
Caenorhabditis elegans, Zebrafish, Tissue culture, Neurotoxicity, Astrocyte, Vanadium, In vitro
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Environmental Exposure*
  • Gene Expression Regulation
  • Nerve Degeneration/etiology*
  • Nerve Degeneration/genetics*
  • Neurotoxicity Syndromes*/complications
  • Neurotoxicity Syndromes*/etiology
  • Neurotoxicity Syndromes*/genetics
  • Neurotoxins/toxicity*
  • Review Literature as Topic
PubMed
20359493 Full text @ Neurotoxicology
Abstract
The understanding of how environmental exposures interact with genetics in central nervous system dysfunction has gained great momentum in the last decade. Seminal findings have been uncovered in both mammalian and non-mammalian model in large result of the extraordinary conservation of both genetic elements and differentiation processes between mammals and non-mammalians. Emerging model organisms, such as the nematode and zebrafish have made it possible to assess the effects of small molecules rapidly, inexpensively, and on a miniaturized scale. By combining the scale and throughput of in vitro screens with the physiological complexity and traditional animal studies, these models are providing relevant information on molecular events in the etiology of neurodegenerative disorders. The utility of these models is largely driven by the functional conservation seen between them and higher organisms, including humans so that knowledge obtained using non-mammalian model systems can often provide a better understanding of equivalent processes, pathways, and mechanisms in man. Understanding the molecular events that trigger neurodegeneration has also greatly relied upon the use of tissue culture models. The purpose of this summary is to provide-state-of-the-art review of recent developments of non-mammalian experimental models and their utility in addressing issues pertinent to neurotoxicity (Caenorhabditis elegans and Danio rerio). The synopses by Aschner and Levin summarize how genetic mutants of these species can be used to complement the understanding of molecular and cellular mechanisms associated with neurobehavioral toxicity and neurodegeneration. Next, studies by Suñol and Olopade detail the predictive value of cultures in assessing neurotoxicity. Suñol and colleagues summarize present novel information strategies based on in vitro toxicity assays that are predictive of cellular effects that can be extrapolated to effects on individuals. Olopade and colleagues describe cellular changes caused by sodium metavanadate (SMV) and demonstrate how rat primary astrocyte cultures can be used as predicitive tools to assess the neuroprotective effects of antidotes on vanadium-induced astrogliosis and demyelination.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping