Medium- and high-throughput screening of neurotoxicants using C. elegans

Boyd, Windy A.; Smith, Marjolein V.; Kissling, Grace E.; Freedman, Jonathan H.

doi:10.1016/j.ntt.2008.12.004

Cited by 100 publications

(80 citation statements)

References 59 publications

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“…While numerous studies have focused on the effects of OPs on C. elegans movement, effects on feeding have also been examined [129,130]. In a study using the OP chlorpyrifos, feeding decreased steadily as the worms were exposed to successively higher concentrations.…”

Section: Feeding Growth and Reproductionmentioning

confidence: 99%

“…EC50 values, concentrations necessary to decrease C. elegans feeding by 50%, ranged from 1.0-2.2 μM [129]. Worms exposed to comparable concentrations of chlorpyrifos also showed greater sensitivity to the pesticide when feeding and/or reproduction were used as endpoints [130,131]. Exposure also results in adverse effects on growth in a concentration dependent manner.…”

Section: Feeding Growth and Reproductionmentioning

confidence: 99%

“…Another OP, parathion, is capable of significantly reducing reproductive output in C. elegans [131]. In reproduction assays using numerous agrochemicals, including diquat and paraquat, parathion more potently inhibited reproduction [129][130][131]. Here, the EC50s related to the reproductive output of C. elegans, determined by counting the number of offspring produced by worms exposed to the compounds from the L4 larval stage to adulthood.…”

Section: Feeding Growth and Reproductionmentioning

confidence: 99%

“…In human astrocytes, expression levels of numerous genes are dysregulated [136,137] and these results have been duplicated in C. elegans [32,104]. Finally, medium and high-throughput screenings utilizing the complex object parametric analyzer and sorter (COPAS) flow sorting system have been used to assess the toxicity of OPs on C. elegans feeding, growth, reproduction and locomotion [130,131]. While this high-throughput technique is not unique to work with OPs, it further demonstrates the ability of using in vitro sorting techniques with a whole model organism to obtain vast quantities of data in relatively short periods of time.…”

Section: Changes In Gene and Protein Expressionmentioning

confidence: 99%

See 3 more Smart Citations

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

McVey

Mink²,

Snapp³

et al. 2012

J Environ Anal Toxicol

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Section: Feeding Growth and Reproductionmentioning

confidence: 99%

Section: Feeding Growth and Reproductionmentioning

confidence: 99%

Section: Feeding Growth and Reproductionmentioning

confidence: 99%

Section: Changes In Gene and Protein Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

McVey

Mink²,

Snapp³

et al. 2012

J Environ Anal Toxicol

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“…Additionally, current high-throughput methods require expensive or specialized equipment [163,[168][169][170][171][172].…”

Section: Introductionmentioning

confidence: 99%

Developing high-throughput methods for C. elegans to better understand the newly discovered gasotransmitter sulfur dioxide

Mathew¹

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Sulfur Dioxide (SO 2 ) is the most recently discovered gasotransmitter. As a result there is a significant gap in the literature compared to the other established gasotransmitters which have had several decades of research. Initially, SO 2 was thought to be a toxic air pollutant and byproduct from the metabolism of sulphur containing amino acids. It is thus important to understand its mechanism of action and molecular targets of SO 2 . The pathways for metabolism of sulfur containing gasotransmitters (hydrogen sulfide and sulfur dioxide) in lower organisms was previously unknown. My thesis goal is to gain a better understanding of the function and metabolism of SO 2 . To better elucidate this function I have used the eukaryotic model organisms; Saccharomyces cerevisiae (S. cerevisiae) and Caenorhabditis elegans (C. elegans).Two high-throughput methods were developed as part of this research to improve detail and accuracy of analysis in C. elegans. The first method developed was WormScan, which allowed for automatic whole organism phenotyping. The second method developed was pHi nanoparticles, to enable the characterization of intracellular pH (pHi). These two C. elegans methods were published in PLOS ONE, 2012 and Analytical Biochemistry, 2014. WormScan is based on an affordable consumer grade flatbed scanner that facilitates the quantification of the four main toxicological endpoints of C. elegans and greatly reduces the user bias associated with manual counting. The light intensity produced by the scanner was sufficient to cause negative phototaxis equivalent to a physical stimulus for mortality determination. The affordability and high-throughput nature of WormScan also enable high-throughput whole animal drug screening in C. elegans. The pHi nanoparticles were generated through a modified Stöber synthesis and easily calibrated externally to the C. elegans. The nanoparticles were taken up during feeding, and found to bypass the selective intestinal uptake and translocate to the primary organs and secondary organs of the reproductive tract. This was the first diagnostic use of nanoparticles in C. elegans.It was found that the hypoxia-inducible factor-1 (hif-1) transcription factor was required in order for C. elegans to survive exposure to SO 2 . HIF-1 is a regulator of both pHi homeostasis and metabolic rate. When C. elegans are exposed to a non-lethal concentration of SO 2 , it induced a reversible state of suspended animation, a condition that is characterized by metabolic suppression. A physiologically relevant drop of 0.15 pH units was observed in response to SO 2 exposure. Where such a decrease in pHi is a characteristic of reduced metabolism.II A forward genetic screen was carried out in C. elegans to identify mutations that conferred resistance to SO 2 . A resistance mutation was mapped to a region of Chromosome III using an as yet unpublished high-throughput technique (Mip-Map). Together with whole genome sequencing the gene F08F8.9 causing resistance was identified. The F08F8.9 gene is hom...

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Neurotoxicology and Behavior

Boyes¹

2012

Patty's Toxicology

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Neurotoxicity is important to consider as a component of occupational and environmental safety and health programs. The failure to do so has contributed to a number of cases in which workers, consumers of manufactured products, and people exposed in the environment were irreparably harmed by exposure to compounds that proved toxic to the nervous system. The field of neurotoxicology originated in response to several episodes of mass poisoning and developed through advances in clinical practice, scientific research, and regulatory actions. This chapter reviews broadly the development of the field of neurotoxicity and discusses some of the predominant current issues. The chapter includes an introduction to the structure and function of the nervous system, the response to injury, the evaluation of sensory, cognitive, and motor functions, and effects on emotionality, mood, and social conduct. Recently, there has been a growing emphasis on potential toxic effects on neurodevelopment and contributions to neurodegenerative diseases. Also, there is a large and growing effort to develop more rapid and cost‐efficient screening tests for potential neurotoxicity. A brief overview of some of the major classes of neurotoxic substances is provided including metals, solvents, pesticides, and persistent organic compounds. Finally, the need for programs to prevent neurotoxic illness is discussed.

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Medium- and high-throughput screening of neurotoxicants using C. elegans

Cited by 100 publications

References 59 publications

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

Developing high-throughput methods for C. elegans to better understand the newly discovered gasotransmitter sulfur dioxide

Neurotoxicology and Behavior

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