|University of Bonn professor Albert Becker|
Professor Albert Becker, his team at the University of Bonn and colleagues at the Hebrew University of Jerusalem have decoded a signaling pathway central to the onset of an epileptic seizure. And they say their work could point the way to developing new drugs that would prevent seizures.
Epilepsy is characterized by the hyperactivity of neural signals in the brain and occurs in up to one in 20 people at least once during their life. Seizures result from the sustained rapid firing of these signals specifically in the temporal lobe of the brain. Ion channels allow the movement of ions such as calcium ions, in and out of neurons, controlling the activity and likelihood of a signal being propagated.
Importantly, a seizure disorder can occur after transient brain damage due to injury or inflammation. "It has also been known for a long time that following transient severe brain injury and prior to an initial spontaneous epileptic seizure, the concentration of free zinc ions increases in the hippocampus. But science has been puzzled about the significance of this phenomenon," says Becker.
In a genetic mouse model, the researchers studied epilepsy in real time making use of a viral vector to deliver fluorescent molecules to neurons. The molecules light up when a calcium channel is activated. The opening of calcium channels gives the researchers information about when and where the animal is having epileptic seizures.
The researchers found that after a transient severe brain damage, zinc ions accumulate and zero in on a genetic switch--metal-regulatory transcription factor 1 (MTF1). This switch turns on the production of calcium channels in neurons, increasing the likelihood these channels will become activated and of the risk that an epileptic seizure will occur.
"Using a genetic method, we inhibited MTF1 in the epileptic mice and as a result, the seizures in the animals were much rarer and weaker," says lead author Dr. Karen van Loo.
They were able to study the effect of MTF1 inhibition in vivo using the fluorescent marker as an indicator of seizure activity. Since there is a lack of effective medicine to prevent epileptic patients from having seizures, this gives hope to the realms of MTF1 inhibition in the clinic.
"About one-third of patients with temporal lobe epilepsy do not respond to medications," says Becker. "Our research is therefore increasingly focusing on new therapeutic options that have few side effects."
The findings of their research were published in the journal Nature Communications this week.