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Originally published as Genetics Published Articles Ahead of Print on February 1, 2008.

Genetics, Vol. 178, 947-956, February 2008, Copyright © 2008
doi:10.1534/genetics.107.082115

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Neuropathology in Drosophila Mutants With Increased Seizure Susceptibility

Tim Fergestad*, Lisa Olson*, Khelan P. Patel*, Rosie Miller{dagger},{ddagger}, Michael J. Palladino{dagger},{ddagger} and Barry Ganetzky*,1

* Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, {dagger} Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 and {ddagger} Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260

1 Corresponding author: Laboratory of Genetics, 425-G Henry Mall, University of Wisconsin, Madison, WI 53706-1580.
E-mail: ganetzky{at}wisc.edu

Genetic 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 ATP{alpha} 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.


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