Genetic and pharmacological manipulations that alter metabolism suppress seizure-like activity in Drosophila

Stone, Bryan D.; Evans, Leah; Coleman, John R.; Kuebler, Daniel

doi:10.1016/j.brainres.2012.12.007

Cited by 13 publications

(11 citation statements)

References 47 publications

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“…The technique described here has been used previously to analyze differences in SLA in the Drosophila BS mutants 1 . The results presented here involve the BS strains easily shocked (eas), bang senseless (bss), and technical knockout (tko).…”

Section: Representative Resultsmentioning

confidence: 99%

“…The bss mutation is an allele of the paralytic (para) voltage-gated sodium channel 17 . The alleles used in this study were eas 1 , bss 1 , and tko 25t . An illustration of the efficacy of the method to measure SLA can be seen in Figure 1, which depicts the path length of a eas seizure-sensitive control fly as compared to one that has been fed the drug metformin.…”

Section: Representative Resultsmentioning

confidence: 99%

“…Given its short lifespan and the robust genetic tools available, Drosophila melanogaster is an excellent model system for investigating the etiology of various diseases and the underlying physiology of various biological processes. In many cases, it is advantageous to measure the effects that behavioral, genetic or pharmacological manipulations have on locomotion in these model organisms 1,2 .…”

Section: Introductionmentioning

confidence: 99%

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A Low-cost Method for Analyzing Seizure-like Activity and Movement in <em>Drosophila</em>

Stone¹,

Burke²,

Pathakamuri³

et al. 2014

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Video tracking systems have been used widely to analyze Drosophila melanogaster movement and detect various abnormalities in locomotive behavior. While these systems can provide a wealth of behavioral information, the cost and complexity of these systems can be prohibitive for many labs. We have developed a low-cost assay for measuring locomotive behavior and seizure movement in D. melanogaster. The system uses a web-cam to capture images that can be processed using a combination of inexpensive and free software to track the distance moved, the average velocity of movement and the duration of movement during a specified time-span. To demonstrate the utility of this system, we examined a group of D. melanogaster mutants, the Bang-sensitive (BS) paralytics, which are 3-10 times more susceptible to seizure-like activity (SLA) than wild type flies. Using this novel system, we were able to detect that the BS mutant bang senseless (bss) exhibits lower levels of exploratory locomotion in a novel environment than wild type flies. In addition, the system was used to identify that the drug metformin, which is commonly used to treat type II diabetes, reduces the intensity of SLA in the BS mutants.

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Section: Representative Resultsmentioning

confidence: 99%

Section: Representative Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Low-cost Method for Analyzing Seizure-like Activity and Movement in <em>Drosophila</em>

Stone¹,

Burke²,

Pathakamuri³

et al. 2014

JoVE

Self Cite

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“…The widely-used bang sensitivity assay, in which several seconds of mechanical stimulation stereotypically induces a pattern of spasm, paralysis, spasm, and recovery (Lee & Wu, 2002; Parker, Howlett, Rusan, & Tanouye, 2011), has been employed for decades to examine seizures at the behavioral and genetic level, helping uncover mechanistic causes of seizures as well as genetic predispositions to and protections from their susceptibility (Benzer, 1971; Ganetzky & Wu, 1982; Howlett, Rusan, Parker, & Tanouye, 2013; Kuebler & Tanouye, 2000; Parker, Padilla, Du, Dong, & Tanouye, 2011; Pavlidis, Ramaswami, & Tanouye, 1994; Stone, Evans, Coleman, & Kuebler, 2013). Furthermore, these behavioral and genetic studies have often been followed up or complemented with electrophysiological studies on the giant fiber (GF) pathway, enabling the understanding of Drosophila seizures at the cellular and circuit level (Elkins & Ganetzky, 1990; Engel & Wu, 1992; Kuebler & Tanouye, 2000; Pavlidis & Tanouye, 1995; Tanouye & Wyman, 1980; Trimarchi & Murphey, 1997).…”

Section: Discussionmentioning

confidence: 99%

The ATP-sensitive K channel is seizure protective and required for effective dietary therapy in a model of mitochondrial encephalomyopathy

Fogle

Hertzler

Palladino

2016

Journal of Neurogenetics

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Effective therapies are lacking for mitochondrial encephalomyopathies (MEs). MEs are devastating diseases that predominantly affect the energy-demanding tissues of the nervous system and muscle, causing symptoms such as seizures, cardiomyopathy, and neuro- and muscular degeneration. Even common anti-epileptic drugs which are frequently successful in ameliorating seizures in other diseases tend to have a lower success rate in ME, highlighting the need for novel drug targets, especially those that may couple metabolic sensitivity to neuronal excitability. Furthermore, alternative epilepsy therapies such as dietary modification are gaining in clinical popularity but haven't been thoroughly studied in ME. Using the Drosophila ATP61 model of ME, we have studied dietary therapy throughout disease progression and found that it is highly effective against the seizures of ME, especially a high fat/ketogenic diet, and that the benefits are dependent upon a functional KATP channel complex. Further experiments with KATP show that it is seizure-protective in this model, and that pharmacological promotion of its open state also ameliorates seizures. These studies represent important steps forward in the development of novel therapies for a class of diseases that is notoriously difficult to treat, and lay the foundation for mechanistic studies of currently existing therapies in the context of metabolic disease.

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“…Investigators have long used the fruit fly as a model for investigations of life span, and accordingly have measured metabolic rate in an often unsuccessful attempt to correlate metabolism to longevity (Arking et al, 1988; Baldal et al, 2006; Hulbert et al, 2004; Khazaeli et al, 2005; Melvin et al, 2007; Miquel et al, 1982; Partridge et al, 2005; Promislow and Haselkorn, 2002; Van Voorhies et al, 2003, 2004b). Metabolic rate in Drosophila has also been investigated in the context of specific genotypes (Hoekstra and Montooth, 2013; Jensen et al, 2014; Jumbo-Lucioni et al, 2010; Montooth et al, 2003; Stone et al, 2013), to reveal how genotype underpins specific metabolic phenotypes. Metabolic rate has also been measured for insight into how specific metabolic pathways affect energy metabolism (Barros et al, 1991; Isobe et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Metabolic rate and hypoxia tolerance are affected by group interactions and sex in the fruit fly (Drosophila melanogaster): new data and a literature survey

Burggren

Souder

2017

Biology Open

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Population density and associated behavioral adjustments are potentially important in regulating physiological performance in many animals. In r-selected species like the fruit fly (Drosophila), where population density rapidly shifts in unpredictable and unstable environments, density-dependent physiological adjustments may aid survival of individuals living in a social environment. Yet, how population density (and associated social behaviors) affects physiological functions like metabolism is poorly understood in insects. Additionally, insects often show marked sexual dimorphism (larger females). Thus, in this study on D. melanogaster, we characterized the effects of fly density and sex on both mass-specific routine oxygen consumption (V̇O2) and hypoxia tolerance (PCrit). Females had significantly lower routine V̇O2 (∼4 µl O2 mg−1 h−1) than males (∼6 µl O2 mg−1 h−1) at an average fly density of 28 flies·respirometer chamber−1. However, V̇O2 was inversely related to fly density in males, with V̇O2 ranging from 4 to 11 µl O2 mg−1 h−1 at a density of 10 and 40 flies·chamber−1, respectively (r2=0.58, P<0.001). Female flies showed a similar but less pronounced effect, with a V̇O2 of 4 and 7 µl O2 mg−1 h−1 at a density of 10 and 40 flies·chamber−1, respectively (r2=0.43, P<0.001). PCrit (∼5.5 to 7.5 kPa) varied significantly with density in male (r2=0.50, P<0.01) but not female (r2=0.02, P>0.5) flies, with higher fly densities having a lower PCrit. An extensive survey of the literature on metabolism in fruit flies indicates that not all studies control for, or even report on, fly density and gender, both of which may affect metabolic measurements.

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Genetic and pharmacological manipulations that alter metabolism suppress seizure-like activity in Drosophila

Cited by 13 publications

References 47 publications

A Low-cost Method for Analyzing Seizure-like Activity and Movement in <em>Drosophila</em>

A Low-cost Method for Analyzing Seizure-like Activity and Movement in <em>Drosophila</em>

The ATP-sensitive K channel is seizure protective and required for effective dietary therapy in a model of mitochondrial encephalomyopathy

Metabolic rate and hypoxia tolerance are affected by group interactions and sex in the fruit fly (Drosophila melanogaster): new data and a literature survey

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