title: Rescue of easily shocked mutant seizure sensitivity in Drosophila adults.
abstract: Genetic factors that influence seizure susceptibility can act transiently during the development of neural circuits or might be necessary for the proper functioning of existing circuits. We provide evidence that the Drosophila seizure-sensitive mutant easily shocked (eas) represents a neurological disorder in which abnormal functioning of existing neural circuits leads to seizure sensitivity. The eas(+) gene encodes for the protein Ethanolamine Kinase, involved in phospholipid biosynthesis. We show that induction of eas(+) in adult mutant flies rescues them from seizure sensitivity despite previously known developmental defects in brain morphology. Additionally, through cell-type-specific rescue, our results suggest a specific role for eas(+) in excitatory rather than inhibitory neural transmission. Overall, our findings emphasize an important role for proper phospholipid metabolism in normal brain function and suggest that certain classes of epilepsy syndromes could have the potential to be treated with gene therapy techniques.
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Kroll
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tanouye
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D003433:Crosses, Genetic; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D055724:Electrophysiological Phenomena; D018869:Heat-Shock Response / Q000235:genetics; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D010743:Phospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); C020125:ethanolamine kinase
keywords: acute; cholinergic; epilepsy; ethanolamine kinase; phospholipids; seizure