Model Mice

Biologist Seyfried and team create new strain that may help solve epilepsy riddle

Epilepsy researchers have known for most of this century that a high-fat diet is effective in preventing epileptic seizures in children, but they don't know why. They recently moved a step closer to understanding the diet's effects when researchers led by Prof. Thomas Seyfried (Biology) developed the first animal model that responds to the diet in a manner similar to that of humans.

Seyfried's team, which has been working with a pediatric neurologist at New England Medical Center and a medical researcher at McLean Hospital, will present its findings at the Society for Neuroscience meeting in Los Angeles on Nov. 10.

The ketogenic diet is a high-fat, low-carbohydrate, low-protein diet that has been used for over 75 years to treat child epileptics who do not respond to medication, according to Seyfried. But little is known about how the diet influences different seizure types or affects a seizure's progression from one spot in the brain to the entire organ.

Prof. Thomas Seyfried (Biology) with Rebecca Madore '99 (left) and graduate student Marianna Todorova. (Photo by Gary Gilbert)
Seyfried, together with doctoral candidate Marianna Todorova and Rebecca Madore '99, has developed a strain of mice that exhibit epilepsy symptoms similar to those in children and young adults. These "EL mice" are the only genetic animal models that express seizure-associated damage to the hippocampus, a region of the brain commonly damaged by epilepsy in humans.

The EL mice are particularly interesting to researchers of human epilepsy, Seyfreid said. "We've never had a natural animal model before," he added. "The epilepsy is not induced by drugs or electroshocks, but is inherited, just as it is in humans. And it parallels many of the features in human epilepsy."

Working with 26 EL mice, Seyfried separated them into a control group and an experimental group. The latter received the ketogenic diet, while the former was fed a standard diet of laboratory mouse chow.

Three weeks into the experiment, the mice were evaluated for their susceptibility to seizures. Seyfried discovered that 92 percent of the control group exhibited generalized seizures, but that none of the mice in the group that had been fed the ketogenic diet experienced a seizure. After eight weeks, half of the experimental mice had generalized seizures, a contrast to the control group which had a seizure rate near 100 percent.

"These are the first findings of an inhibitory effect of the ketogenic diet on epilepsy in a genetic model and indicate that the EL mouse will be useful for evaluating the anti-seizure mechanisms of the ketogenic diet," said Seyfried. "Moreover, the findings can be extended to determine if the ketogenic diet might influence neural development and protect the brain from seizure-associated neuronal damage. The results from this study will have broad significance for clinical neurology and basic neuroscience."

-Michael Seele

Return to Oct. 29 menu

Return to Chronicle home page