Genetics. Published Articles Ahead of Print: February 1, 2008, Copyright © 2008
doi:10.1534/genetics.107.082115


A more recent version of this article appeared on February 1, 2008.

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Neuropathology in Drosophila Mutants With Increased Seizure Susceptibility

Tim Fergestad 1, Lisa Olson 2, Khelan P. Patel 2, Rosie Miller 3, Michael J. Palladino 3 and Barry Ganetzky 4*

1 University of Wisconsin - Madison
2 University of Wisconsin-Madison
3 University of Pittsburgh
4 University of Wisconsin

* To whom correspondence should be addressed. E-mail: ganetzky{at}wisc.edu.

Submitted on September 20, 2007
Revised on November 13, 2007
Accepted on 1 December 2007


Abstract

GGenetic factors are known to contribute to seizure susceptibility, although the long-term effects of these predisposing factors on neuronal viability remain unclear. To examine the consequences of genetic factors conferring increased seizure susceptibility, we surveyed a class of Drosophila mutants that exhibit seizures and paralysis following mechanical stimulation. These bang-sensitive seizure mutants exhibit shortened life spans and age-dependent neurodegeneration. Because the increased seizure susceptibility in these mutants likely results from altered metabolism and since the Na+/K+ ATPase consumes the majority of ATP in neurons, we examined the effect of ATPalpha mutations in combination with bang-sensitive mutations. We found that double mutants exhibit strikingly reduced life spans and age-dependent uncoordination and inactivity. These results emphasize the importance of proper cellular metabolism in maintaining both the activity and viability of neurons.

Key Words: ATPalpha, bang-sensitive mutants, epilepsy, metabolism, neurodegeneration