Use of non-mammalian alternative models for neurotoxicological study

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
NeuroToxicology (Impact Factor: 3.38). 06/2008; 29(3):546-55. DOI: 10.1016/j.neuro.2008.04.006
Source: PubMed


The field of neurotoxicology needs to satisfy two opposing demands: the testing of a growing list of chemicals, and resource limitations and ethical concerns associated with testing using traditional mammalian species. National and international government agencies have defined a need to reduce, refine or replace mammalian species in toxicological testing with alternative testing methods and non-mammalian models. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expense and using fewer mammals. Recent advances in genetic technologies and the strong conservation between human and non-mammalian genomes allow for the dissection of the molecular pathways involved in neurotoxicological responses and neurological diseases using genetically tractable organisms. In this review, applications of four non-mammalian species, zebrafish, cockroach, Drosophila, and Caenorhabditis elegans, in the investigation of neurotoxicology and neurological diseases are presented.

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    • "Doing so will aid in implementing the use of in vitro data for REACH and other legislative frameworks (Bal-Price et al., 2008, 2010; Llorens et al., 2012; van Thriel et al., 2012). Combined with validation of the (biological) relevance of the in vitro observed effects in alternative species (Levin et al., 2009; Peterson et al., 2008), the increase in in vitro data will ultimately pave the way for further implementation of in silico data in legislative frameworks as suggested by Dr. Zarros. "

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    • "The straightforward generation of knockout strains for genes of interest and of transgenic worms expressing green fluorescent protein (GFP)-tagged proteins make it an ideal model for expression or protein localization studies (Chalfie et al., 1994; Gerstein et al., 2010; Helmcke et al., 2010). The short life-cycle, easy and inexpensive maintenance, and detailed characterization of the complete cell lineage (zygote to adult) allow the utilization of rapid, low-cost tests that readily lend themselves to mechanistic studies of toxicant action (Peterson et al., 2008), including Mn-induced toxicity (Benedetto et al., 2010). Exposure to excessive Mn levels, increased brain Mn deposition leads to dopaminergic (DAergic) neurodegeneration and an extrapyramidal syndrome referred to as manganism, which shares multiple clinical features with Parkinson's disease (PD) (Benedetto et al., 2010). "
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    • "It is also having wide applications in the investigation of cancer, heart diseases, neurological malfunctions, behavioral diseases and to observe the mutations and problems in organ development due to exposure to test molecules. Modeling of certain human diseases in zebra fish could be used to ameliorate the disease phenotype and malfunctions in organ development (Peterson et al., 2008). "
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