title: Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.
abstract: Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
authors: Zeid M
authors: ZM
authors: Rusan
authors: Department of Environmental Science, Policy and Management, University of California, Berkeley, California, United States of America.
authors: Olivia A
authors: OA
authors: Kingsford
authors: Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America; Department of Environmental Science, Policy and Management, University of California, Berkeley, California, United States of America; Helen Wills Neuroscience Institute, University of California, Berkeley, California, United States of America.
authors: Mark A
authors: MA
authors: Tanouye
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000473:pathology / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D012640:Seizures / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D027981:Symporters; D000096922:K Cl- Cotransporters