ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Seizure suppression by top1 mutations in Drosophila.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 29 citations in OpenAlex.
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- Dynamic localization of DNA topoisomerase I and its functional relevance during Drosophila development.G3 (Bethesda, Md.) · 2021Article
- Investigating rare and ultrarare epilepsy syndromes withFaculty reviews · 2021Review
- Investigating Developmental and Epileptic Encephalopathy UsingInternational journal of molecular sciences · 2020Review
- A Systematic Review on Non-mammalian Models in Epilepsy Research.Frontiers in pharmacology · 2018Article
- Seizure Suppression by High Temperature via cAMP Modulation in Drosophila.G3 (Bethesda, Md.) · 2016Article
- Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila.PLoS genetics · 2016Article
- Drosophila sodium channel mutations: Contributions to seizure-susceptibility.Experimental neurology · 2015Review
- Disruption of Endocytosis with the Dynamin Mutant shibirets1 Suppresses Seizures in Drosophila.Genetics · 2015Article
- Seizure suppression through manipulating splicing of a voltage-gated sodium channel.Brain : a journal of neurology · 2015Article
- Genome-wide screen for modifiers of Na (+) /K (+) ATPase alleles identifies critical genetic loci.Molecular brain · 2014Article
- Topoisomerase 1 inhibition reversibly impairs synaptic function.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Susceptibility to ethanol withdrawal seizures is produced by BK channel gene expression.Addiction biology · 2014Article
- A knock-in model of human epilepsy in Drosophila reveals a novel cellular mechanism associated with heat-induced seizure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Neuroprotection by spice-derived nutraceuticals: you are what you eat!Molecular neurobiology · 2011Review
- Seizure and epilepsy: studies of seizure disorders in Drosophila.International review of neurobiology · 2011Review
- Drosophila melanogaster as a model organism of brain diseases.International journal of molecular sciences · 2009Review
- A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs.BMC systems biology · 2009Article
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3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA topoisomerase I is an essential nuclear enzyme involved in resolving the torsional stress associated with DNA replication, transcription, and chromatin condensation. Here we report the discovery of a seizure-suppressor mutant, top1(JS), which suppresses seizures in a Drosophila model of human epilepsy. A P-element mutagenesis screen using easily shocked seizure-sensitive mutant as a genetic background identified top1(JS), which plays a novel role in regulating nervous system excitability. Plasmid rescue, excision, complementation, and sequencing analyses verified that top1(JS) results from a P-element insertion in the 5' untranslated region. Quantitative reverse transcription analysis on wild-type and mutant fly heads showed that the top1(JS) mutation causes reduced transcription level in the CNS, suggesting a partial loss-of-function mutation. Electrophysiological experiments revealed normal seizure thresholds in top1(JS) mutants, which are different from other seizure suppressors identified previously, suggesting a novel mechanism underlying seizure suppression by top1(JS). The pharmacological camptothecin feeding experiment and cell death analysis suggested that the seizure suppression by top1(JS) may occur via increased neuronal apoptosis. Furthermore, overexpression of the DIAP1 (Drosophila inhibitor of apoptosis 1) gene rescues top1(JS) suppression, providing additional support for a neural apoptosis suppression mechanism. The top1(JS) mutation is the first viable partial loss-of-function mutation identified in higher eukaryotes, and the results presented here point to a novel function for topo I in construction and/or maintenance of circuits required for seizure propagation in vivo.
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