PgmNr D1379: A Ketogenic Dietary Supplement Eliminates Seizure-Like Activity and Paralysis in the Bang-sensitive (BS) Paralytic Mutants.

Authors:
M. Nelson; C. Radlicz; J. Rubera; T. Taylor; A. Chambers; C. Bittner; D. Kuebler


Institutes
Franciscan University of Steubenville, Steubenville, OH.


Keyword: neural disorder

Abstract:

The Drosophila Bang-sensitive (BS) paralytic mutants undergo seizure-like activity  (SLA) and paralysis following a variety of insults such as mechanical shock. While the etiology underlying this defect is poorly understood, a number of recent studies in our lab have demonstrated that metabolic and dietary alterations can suppress, but not complete eliminate, SLA and paralysis in these mutants. Given that a ketogenic diet is known to reduce seizures in many children with refractory epilepsy, we examined the effect this diet had on the BS mutants easily-shocked (eas), bang-senseless (bss), and technical knockout (tko). These mutants were fed a standard cornmeal/yeast/sugar diet supplemented with 10% KetoCal 4:1, a commercially available ketogenic formula consisting of a 4:1 ratio of fats to carbohydrates.  Newly eclosed BS flies were fed this diet for 3, 5 or 7 days and all three genotypes displayed significant reductions in SLA and paralysis following mechanical shock. After only 3 days on the diet, over 90% of tko flies no longer exhibited SLA or paralysis, and complete suppression of the BS phenotype was seen by day 7. In the case of eas, only 30% still displayed SLA after 3 days on the diet and SLA was completely suppressed by day 7.  The bss flies showed a similar but less robust reduction of SLA on the diet as 35% of flies still exhibited SLA and paralysis following 7 days on the diet. In addition to reducing SLA, the diet partially rescued the reduction in basal activity that is normally seen in the BS mutants.  Taken together, the data indicates that the BS mutants represent an attractive model for investigating the underlying mechanism by which the ketogenic diet can suppress seizures.



Flybase Genetic Index:
1. FlyBase gene symbol: eas; FBgn: FBgn0000536
2. FlyBase gene symbol: bss (para); FBgn: FBgn0264255
3. FlyBase gene symbol: tko; FBgn: FBgn0003714