A new model to study sleep deprivation-induced seizure

Sleep. 2015 May 1;38(5):777-85. doi: 10.5665/sleep.4674.

Abstract

Background and study objectives: A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation.

Design: Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB(9ed4)), and in an adult temperature sensitive seizure mutant seizure (sei(ts1)) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB(9ed4) flies was also assessed.

Setting: Laboratory.

Participants: Drosophila melanogaster.

Interventions: Sleep deprivation.

Measurements and results: Sleep deprivation increased seizure susceptibility in adult sesB(9ed4)/+ and sei(ts1) mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB(9ed4)/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB(9ed4)/+ became adults.

Conclusions: These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity.

Keywords: Drosophila melanogaster; seizure; sleep homeostasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology
  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use
  • Disease Models, Animal*
  • Disease Susceptibility
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster* / drug effects
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / growth & development
  • Drosophila melanogaster* / physiology
  • Female
  • Male
  • Mitochondrial ADP, ATP Translocases / genetics
  • Mitochondrial ADP, ATP Translocases / metabolism
  • Mutation / genetics
  • Phenotype
  • Seizures / drug therapy
  • Seizures / etiology*
  • Seizures / genetics
  • Seizures / physiopathology*
  • Sleep / genetics
  • Sleep Deprivation / complications*
  • Sleep Deprivation / genetics
  • Sleep Deprivation / physiopathology*
  • Temperature
  • Time Factors
  • Valproic Acid / pharmacology
  • Valproic Acid / therapeutic use

Substances

  • Anticonvulsants
  • Drosophila Proteins
  • sesB protein, Drosophila
  • Valproic Acid
  • Mitochondrial ADP, ATP Translocases