An automated method to assay locomotor activity in third instar Drosophila melanogaster larvae

Graham, Stephanie M.; Rogers, Ryan; Alper, Richard H.

doi:10.1016/j.vascn.2015.10.004

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…There are previous reports showing alterations in either larval locomotion or peristaltic wave frequency in seizure susceptible Drosophila mutants (Graham et al, 2016;Stilwell et al, 2006;Streit et al, 2016). We decided to test for such in the range of mutants used for this study and compare that to the results of adult activity.…”

Section: Bang-sensitive Mutants Show Reduced Larval Locomotionmentioning

confidence: 99%

Characterization of Seizure Induction Methods inDrosophila

Mituzaite

Petersen

Claridge‐Chang

et al. 2021

eNeuro

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Epilepsy is one of the most common neurological disorders. Around one third of patients do not respond to current medications. This lack of treatment indicates a need for better understanding of the underlying mechanisms and, importantly, the identification of novel targets for drug manipulation. The fruitfly Drosophila melanogaster has a fast reproduction time, powerful genetics, and facilitates large sample sizes, making it a strong model of seizure mechanisms. To better understand behavioural and physiological phenotypes across major fly seizure genotypes we systematically measured seizure severity and secondary behavioral phenotypes at both the larval and adult stage. Comparison of several seizure-induction methods; specifically electrical, mechanical and heat-induction, show that larval electroshock is the most effective at inducing seizures across a wide range of seizure-prone mutants tested. Locomotion in adults and larvae was found to be nonpredictive of seizure susceptibility. Recording activity in identified larval motor neurons revealed variations in action potential patterns, across different genotypes, but these patterns did not correlate with seizure susceptibility. To conclude, while there is wide variation in mechanical induction, heat induction, and secondary phenotypes, electroshock is the most consistent method of seizure induction across known major seizure genotypes in Drosophila. 4 Significance StatementEpilepsy is a neurological disorder affecting 1 in 130 people globally, with a significant impact on patients, families, and society. Approximately one third of epileptics do not respond to currently available medication. Thus, better insights into underlying disease mechanisms and identification of new drugs are needed. Fruit flies (Drosophila melanogaster) are a powerful genetic model: a number of single gene mutant flies exhibit seizures, phenotypes that have been shown to respond to established antiepileptic drugs.We compare methods of seizure induction and their utility, to establish which induction method is the most consistent across a range of different seizure-inducing genetic backgrounds. Adopting a common method for seizure analysis in this model will, we predict, speed identification of novel anti-convulsive treatments.

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Section: Bang-sensitive Mutants Show Reduced Larval Locomotionmentioning

confidence: 99%

Characterization of Seizure Induction Methods inDrosophila

Mituzaite

Petersen

Claridge‐Chang

et al. 2021

eNeuro

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“…Drosophila adult activity was collected and analyzed using the animal behaviour trajectory tracking system, DanioVision (DVOL-0040, Noldus Information Technology, The Netherlands), and Ethovision XT software (Noldus Information Technology). 17…”

Section: Behavioural Assaysmentioning

confidence: 99%

Lactobacillus reuteri's multifaceted role in mitigating ionizing radiation-induced injury inDrosophila melanogaster

Zhang,

Wang,

Jiang

et al. 2024

Food Funct.

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“…Semiautomated commercial systems are available that quantify fish swimming patterns and distance traveled over minutes to hours under basal or stressed conditions in a 96-well plate format allowing diverse therapies to be compared in 1 week old zebrafish larvae. 62,63 In addition, some disorders have focused symptom burden in specific organs, such as metabolic strokes in the brain, cardiomyopathy or arrhythmias in the heart, and vision loss from retinal or optic nerve problems. 40,64 While C. elegans are useful for interrogation of integrated physiology at the level of development, fecundity, neuromuscular activity, and survival, 65 zebrafish provide the advantage of being vertebrate animals with discrete organs including brain, eyes, otic vesicle, heart, liver, kidney, intestinal tract, skeletal muscle, and swim bladder.…”

Section: High-throughput Drug Screen: Rationale and Approachmentioning

confidence: 99%

“…More generally useful in zebrafish are swimming activity assays, which correlate well with the prioritized mitochondrial disease patient outcomes of fatigue and exercise capacity. Semiautomated commercial systems are available that quantify fish swimming patterns and distance traveled over minutes to hours under basal or stressed conditions in a 96‐well plate format allowing diverse therapies to be compared in 1 week old zebrafish larvae 62,63 …”

Section: Introductionmentioning

confidence: 99%

The pursuit of precision mitochondrial medicine: Harnessing preclinical cellular and animal models to optimize mitochondrial disease therapeutic discovery

Falk

2020

J of Inher Metab Disea

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Mitochondria share extensive evolutionary conservation across nearly all living species. This homology allows robust insights to be gained into pathophysiologic mechanisms and therapeutic targets for the heterogeneous class of primary mitochondrial diseases (PMDs) through the study of diverse in vitro cellular and in vivo animal models. Dramatic advances in genetic technologies, ranging from RNA interference to achieve graded knock‐down of gene expression to CRISPR/Cas‐based gene editing that yields a stable gene knock‐out or targeted mutation knock‐in, have enabled the ready establishment of mitochondrial disease models for a plethora of individual nuclear gene disorders. These models are complemented and extended by the use of pharmacologic inhibitor‐based stressors to characterize variable degrees, onset, duration, and combinations of acute on chronic mitochondrial dysfunction in individual respiratory chain enzyme complexes or distinct biochemical pathways within mitochondria. Herein is described the rationale for, and progress made in, “therapeutic cross‐training,” a novel approach meant to improve the validity and rigor of experimental conclusions when testing therapies by studying treatment effects in multiple, evolutionarily‐distinct species, including Caenorhabditis elegans (invertebrate, worm), Danio rerio (vertebrate, zebrafish), Mus musculus (mammal, mouse), and/or human patient primary fibroblast cell line models of PMD. The goal of these preclinical studies is to identify lead therapies from candidate molecules or library screens that consistently demonstrate efficacy, with minimal toxicity, in specific subtypes of mitochondrial disease. Conservation of in vitro and in vivo therapeutic effects of lead molecules across species has proven extensive, where molar concentrations found to be toxic or efficacious in one species are often consistent with therapeutic effects at similar doses seen in other mitochondrial disease models. Phenotypic outcome studies in all models are prioritized at the level of survival and function, to reflect the ultimate goal of developing highly potent therapies for human mitochondrial disease. Lead compounds that demonstrate significant benefit on gross phenotypes may be further scrutinized in these same models to decipher their cellular targets, mechanism(s), and detailed biochemical effects. High‐throughput, automated technologic advances will be discussed that enable efficient, parallel screening in a diverse array of mitochondrial disease disorders and overarching subclasses of compounds, concentrations, libraries, and combinations. Overall, this therapeutic cross‐training approach has proven valuable to identify compounds with optimal potency and safety profiles among major biochemical subtypes or specific genetic etiologies of mitochondrial disease. This approach further supports rational prioritization of lead compounds, target concentrations, and specific disease phenotypes, outcomes, and subgroups to optimally inform the design of clinical trials that test ...

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An automated method to assay locomotor activity in third instar Drosophila melanogaster larvae

Cited by 7 publications

References 8 publications

Characterization of Seizure Induction Methods inDrosophila

Characterization of Seizure Induction Methods inDrosophila

Lactobacillus reuteri's multifaceted role in mitigating ionizing radiation-induced injury inDrosophila melanogaster

The pursuit of precision mitochondrial medicine: Harnessing preclinical cellular and animal models to optimize mitochondrial disease therapeutic discovery

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