25 November 2020
Fruitfly study unveils secrets of epileptic seizures
Published online 10 August 2014
Epilepsy has been linked to mutations in a human gene known as PRICKLE. However, it is not known how they trigger epileptic seizures in humans and other animals.
Now, a team of researchers from University of Iowa, USA, and King Abdullah International Medical Research Centre, Saudi Arabia, has discovered that mutations in the prickle gene in fruitfly alter the balance of certain proteins. This disrupts the activity of fruitfly neurons, which in turn causes seizures. They reported their findings in Proceedings of the National Academy of Sciences1.
The researchers induced mutations in the prickle gene in test fruit flies. The mutant flies had reduced levels of either of two Prickle proteins, Prickle-spiny-legs or Prickle-prickle. They then showed that short electrical pulses across the fruitfly brain triggered seizure discharges in adult flies that had reduced levels of spiny-legs prickle protein.
The researchers found that the mutant spiny-legs flies were prone to seizures. These mutant flies showed enhanced transport of vesicles inside neurons. Altering the balance of two Prickle proteins can disrupt vesicle transport and tipping the balance in one direction predisposed flies to seizures.
In addition, they found that lowering the levels of specific motor proteins that transport vesicles in fruitfly neurons could suppress prickle-mediated seizure. “With potential drug targets such as prickle proteins and vesicle-transport motor proteins identified, fruitfly model seems a simple and cost-effective way to screen potential drug molecules with anti-epileptic properties,” says John Manak, a senior author of the study.
- Ehaideb, S. N. et al. prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies. Proc. Natl Acad. Sci. USAhttp://dx.doi.org/10.1073/pnas.1403357111 (2014)