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PLoS One. 2014 Jun 27;9(6):e101117. doi: 10.1371/journal.pone.0101117. eCollection 2014.

Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

Author information

1
Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
2
Department of Environmental Science, Policy and Management, University of California, Berkeley, California, United States of America.
3
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.

Erratum in

  • PLoS One. 2014;9(9):e108081.

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.

PMID:
24971529
PMCID:
PMC4074161
DOI:
10.1371/journal.pone.0101117
[Indexed for MEDLINE]
Free PMC Article

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