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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. "
    NeuroToxicology 09/2014; 44. DOI:10.1016/j.neuro.2014.06.004 · 3.38 Impact Factor
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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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    ABSTRACT: Organochalcogens are promising pharmacological agents that possess significant biological activities. Nevertheless, because of the complexity of mammalian models, it has been difficult to determine the molecular pathways and specific proteins that are modulated in response to treatments with these compounds. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging and in vivo live analysis of toxicity. Abundant evidence points to oxidative stress in mediating manganese (Mn)-induced toxicity. In this study we challenged worms with Mn, and investigated the efficacy of inedited selenium- and tellurium- xylofuranosides in reversing and/or protecting the worms from Mn-induced toxicity. In addition, we investigated their putative mechanism of action. First, we determined the lethal dose 50% (LD50) and the effects of the xylofuranosides on various toxic parameters. This was followed by studies on the ability of xylofuranosides to afford protection against Mn-induced toxicity. Both Se- and Te-xylofuranosides increased the expression of superoxide dismutase (SOD-3). Furthermore, we observed that the xylofuranosides induced nuclear translocation of the transcription factor DAF-16/FOXO, which in the worm is known to regulate stress responsiveness, aging and metabolism. These findings suggest that xylofuranosides attenuate toxicity Mn-induced, by regulating the DAF-16/FOXO signaling pathway.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2013; 64. DOI:10.1016/j.fct.2013.11.030 · 2.90 Impact Factor
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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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    ABSTRACT: The number of animals used in research has increased with the advancement of research and development in medical technology. Every year, millions of experimental animals are used all over the world. The pain, distress and death experienced by the animals during scientific experiments have been a debating issue for a long time. Besides the major concern of ethics, there are few more disadvantages of animal experimentation like requirement of skilled manpower, time consuming protocols and high cost. Various alternatives to animal testing were proposed to overcome the drawbacks associated with animal experiments and avoid the unethical procedures. A strategy of 3 Rs (i. e. reduction, refinement and replacement) is being applied for laboratory use of animals. Different methods and alternative organisms are applied to implement this strategy. These methods provide an alternative means for the drug and chemicals testing, up to some levels. A brief account of these alternatives and advantages associated are discussed in this review with examples. An integrated application of these approaches would give an insight in to minimum use of animals in scientific experiments.
    Saudi Pharmaceutical Journal 11/2013; 1(3). DOI:10.1016/j.jsps.2013.11.002 · 1.28 Impact Factor
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