Logo for University of Iowa Health Care This logo represents the University of Iowa Health Care

Chance observation leads to seizure-suppressing discovery in fruit fly model

A few years ago, Toshihiro Kitamoto, PhD, and a colleague in the Biology Department, Chun-Fang Wu, PhD, noticed that fly mutants, which Kitamoto’s lab was using as a fly model of epilepsy, were significantly less susceptible to seizures when they were raised on the east side of the river in the Biology lab. Unable to explain the difference, he asked what food the flies had been given in the Biology Department.

“There are various ‘standard’ foods for fruit flies used for research,” Kitamoto, associate professor of anesthesia and pharmacology at the University of Iowa, says. “Flies in my lab had been fed one kind of food, and those in Biology had been fed a different kind. So we looked at the two foods and discovered that one of them contained milk whey.”

Toshihiro Kitamoto Toshihiro Kitamoto, PhD

Milk whey is what remains after milk curdles – a complex mixture of proteins, carbohydrates, fats, vitamins, and minerals. The fruit flies that were less susceptible to seizure-inducing stimuli were given the food containing milk whey.

That chance observation led Kitamoto and colleagues at the University of Iowa to conduct a series of tests to see whether milk whey really influenced neurological development and behavior in fruit flies.

Certain types of fruit flies are good models for epilepsy in humans, because the basic molecular and cellular mechanisms controlling development and function of the nervous system are evolutionarily well conserved between flies and humans. The specific types of fruit flies that Kitamoto and his colleagues used for the milk whey study had several characteristics caused by hyperexcitability of the nervous system: wings that turned down instead of folding over the back, spontaneous tremors, and heat-induced seizures.

The study found that incidence of these characteristics was significantly lessened when the flies were fed a diet that included milk whey during the developmental, or larval, stage.

For example, when larvae were fed a diet without milk whey, as many as 7 in 10 had down-turned wings when they emerged from the pupal stage, and their turn angle when walking was nearly 110 degrees, which the researchers attributed to lack of coordination and frequent spasms.

However, when larvae were fed a diet with milk whey, only 2 in 10 had down-turned wings, and their turn angle was about 45 degrees, statistically indifferent from the average turn angle of normal fruit flies.

The “recovery” effect of milk whey was most dramatic during the developmental stage, and the researchers emphasized that starting a milk-whey diet in adulthood appeared to have little effect on the flies.

Much remains to be studied. For example, although there are clues, researchers still don’t know exactly which specific components are responsible for the changes they observed, and it is unclear how milk whey affects development of the nervous system.

“Even since the time of Hippocrates, we have known that diet and nutrition have a marked effect on epilepsy. In fact, dietary approaches, such ketogenic diet (KD), are efficient to prevent or treat epilepsy. However, use of the KD is not feasible for a subset of patients because of its highly restrictive nutritional guidelines,” Kitamoto says. “This finding provides a solid foundation for further investigation into how simple dietary supplementation affects development and function of the nervous system and, ultimately, how they influence behavior.”

The paper is Milk-whey diet substantially suppresses seizure-like phenotypes of paraShu, a Drosophila voltage-gated sodium channel mutant, published in the Journal of Neurogenetics.


Monday, August 26, 2019