Use of non-mammalian alternative models for neurotoxicological study

Abstract

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 allows 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.

Reply on ‘Prerequisites for a reliable introduction of in vitro neurotoxicity testing within the REACH framework’

“…Doing so will aid in implementing the use of in vitro data for REACH and other legislative frameworks (Bal-Price et al, 2008, 2010Llorens 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.…”

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

“…Starting in the mid 1990s C. elegans became a more widely-used model in the neurotoxicology community [3,29,31,33]. This was partly due to the simplicity of their nervous system, which is a relatively small neuronal network that is highly stereotypical from animal to animal [6].…”

“…More recently, C. elegans has proven to be a beneficial model organism for studies of major pesticides classes, including organophosphates (OPs) and dithiocarbamates (DTCs). Using C. elegans, scientists can study the various effects these agrochemicals may exert on humans [3,[29][30][31]. For example, in a study involving OPs and C. elegans, alterations in gene and protein expression were examined [32], particularly nervous system-specific endpoints.…”

Current standing and future prospects for the technologies proposed to transform toxicity testing in the 21st century

“…The fly has been used as a model to study neurodegenerative disease and its drug discovery (Bilen and Bonini, 2005;Lu, 2009;Nichols, 2006). Testing adult or developmental neurotoxicity also seems particularly promising (Peterson et al, 2008;Rand, 2010). A number of endpoints can be measured in the fruit fly that provide information on toxicity, such as lethality, adult morphology, behavior, and reporter gene or protein expression.…”