Neuropathology in Drosophila mutants with increased seizure susceptibility.
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 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.
Fergestad
Tim
T
Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA.
Olson
Lisa
L
Patel
Khelan P
KP
Miller
Rosie
R
Palladino
Michael J
MJ
Ganetzky
Barry
B
D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D020022:Genetic Predisposition to Disease; D008136:Longevity; D009154:Mutation; D009420:Nervous System / Q000473:pathology; D012640:Seizures / Q000235:genetics*