Drosophotoxicology: The growing potential for Drosophila in neurotoxicology

Abstract

Understanding neurotoxic mechanisms is a challenge of deciphering which genes and gene products in the developing or mature nervous system are targeted for disruption by chemicals we encounter in our environment. Our understanding of nervous system development and physiology is highly advanced due in large part to studies conducted in simple non-mammalian models. The paucity of toxicological data for the more than 80,000 chemicals in commercial use today, and the approximately 2,000 new chemicals introduced each year, make development of sensitive and rapid assays to screen for neurotoxicity paramount. In this article I advocate the use of Drosophila in the modern regimen of toxicological testing, emphasizing its unique attributes for assaying neurodevelopment and behavior. Features of the Drosophila model are reviewed and a generalized overall scheme for its use in toxicology is presented. Examples of where the fly has proven fruitful in evaluating common toxicants in our environment are also highlighted. Attention is drawn to three areas where development and application of the fly model might benefit toxicology the most: 1) optimizing sensitive endpoints for pathway-specific screening, 2) accommodating high throughput demands for analysis of chemical toxicant libraries, 3) optimizing genetic and molecular protocols for more rapid identification toxicant-by-gene interactions. While there are shortcomings in the Drosophila model, which exclude it from effective toxicological testing it certain arenas, conservation of fundamental cellular and developmental mechanisms between flies and man are extensive enough to warrant a central role for the Drosophila model in toxicological testing of today.

Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster

“…Rotenone (ROT), a well-established mitochondrial toxin is often used as a model chemical, since it reproduces some important aspects of PD pathology both in Drosophila and rodent models (Coulom and Birman, 2004;Canon and Greenamyere 2010). In this regard, the use of Drosophila as a PD model is rather well accepted by numerous researchers (Hirth 2010;Rand, 2010). Earlier our findings have shown the advantages and reproducibility of the ROT model and the efficacy of select medicinal plant extracts and spice active principles to attenuate oxidative stress and neurotoxicity in the Drosophila system (Hosamani and Muralidhara, 2009;Girish and Muralidhara, 2012;Prasad and Muralidhara, 2012).…”

Effect of dietary inclusions of bitter kola seed on geotactic behavior and oxidative stress markers in Drosophila melanogaster

“…Indeed, cellular macromolecules are protected primarily from the insult of free radical species by endogenous antioxidant molecules including catalase, glutathione peroxidase, glutathione‐S‐transferase, and superoxide dismutase (Rand, 2010). Catalase catalyzes the reduction of H 2 O 2 to H 2 O and O 2 and thus protects biological tissues from the deleterious peroxidative effect of H 2 O 2 (Abolaji, Olaiya, Oluwadahunsi, & Farombi, 2017).…”

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.…”

“…The first is that the demand for toxicological information on chemicals now is largely exceeding the ability to produce relevant data based on the current regulatory animal tests. At present, there are about 80,000 chemicals on the market, and each year about 2,000 new chemicals are introduced for which there is limited or no adequate toxicological information (US EPA, 1998a,b;Bakand et al, 2005;Grandjean and Landrigan, 2006;Rand, 2010). The second reason is that our society is increasingly less willing to accept risks in consumer products or in the environment.…”