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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Brain Research
Article . 2013 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Genetic and pharmacological manipulations that alter metabolism suppress seizure-like activity in Drosophila

Authors: Bryan, Stone; Leah, Evans; John, Coleman; Daniel, Kuebler;

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

Abstract

There is increasing evidence that alterations in metabolism can affect seizure susceptibility in a wide range of organisms. In order to investigate the link between metabolism and seizures, we took advantage of a group of Drosophila mutants, the Bang-sensitive (BS) paralytics, which are 3-10 times more susceptible to seizure-like activity (SLA) than wild type flies following a variety of stimuli including mechanical shock. To alter metabolism, we introduced the atsugari (atu) mutation into three of the BS mutants, easily shocked (eas), bang senseless (bss), and technical knockout (tko). The atu mutants, which exhibit reduced expression of the Drosophila ortholog of dystroglycan gene, have previously been shown to have a higher metabolic rate than wild type flies. Following mechanical shock, all three BS;atu double mutants displayed a reduction in SLA and the eas;atu and tko;atu double mutants recovered from the shock quicker than the respective single mutant BS flies. In addition, the eas;atu and tko;atu flies displayed higher levels of metabolism as compared to the single mutant BS flies. To further study the correlation between metabolism and seizure susceptibility, the three BS strains were fed a sulfonylurea drug (tolbutamide) known to both increase heamolymph glucose concentrations and stimulate lipid metabolism in flies. Following mechanical shock, the eas and tko mutants fed tolbutamide displayed less SLA and recovered quicker than unfed flies. While the bss mutants fed tolbutamide did not display a reduction in SLA, they did recover quicker than unfed controls. These data indicate that the upregulation of metabolism can have a protective effect against seizure susceptibility, a result that suggests new avenues for possible drug development.

Related Organizations
Keywords

Male, Time Factors, Tolbutamide, Recovery of Function, Carbon Dioxide, Statistics, Nonparametric, Animals, Genetically Modified, Disease Models, Animal, Seizures, Physical Stimulation, Mutation, Animals, Drosophila Proteins, Hypoglycemic Agents, Drosophila, Disease Susceptibility, Stress, Mechanical, Locomotion

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    14
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    Top 10%
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    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
14
Top 10%
Average
Top 10%