Fluorescence in the brain of a living mouse: The emanating beams of light can be measured through the top of the skulls. The degree of fluorescence is reflected through colors, whereby the intensity decreases from red to violet. Credit: © Image: Karen von Loo/Laboratory of Albert Becker
If they blocked a central switch in epileptic mice, the frequency and severity of the seizures decreased. Using a novel technology, it was possible to observe the processes prior to the occurrence of epileptic seizures in living animals. About 1 of 20 people in the course of his or her life suffers an epileptic attack, during which the nerve cells get out of their usual rhythm and fire in a very rapid frequency. This results in seizures. Such synchronous discharges in the brain occur most frequently in the temporal lobe. Often, a seizure disorder develops after a delay following transient brain damage – eg due to injury or inflammation. Ion channels regulate the entry of calcium ions in the nerve cells.
“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 Prof. Dr. Albert J. Becker.
The team have now decoded a signaling pathway which is involved in the onset of a seizure disorder. If the number of zinc ions increases following transient severe brain damage, these ions dock in greater numbers onto a switch, the so-called metal-regulatory transcription factor 1 (MTF1). This leads to a large increase in the amount of a special calcium ion channel in the nerve cells and overall, this significantly boosts the risk of epileptic seizures.
Transcription factor MTF1 plays a central role in this connection using an experiment on mice suffering from epilepsy. “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 Dr. Karen M.J. van Loo.
With the help of viruses, the researchers introduced fluorescing molecules in the brains of mice and these molecules always glowed when the production of the special calcium ion channel was activated. The beams of light emanating from the fluorescence molecules can be measured through the top of the mice’s skulls. This makes it possible to examine the processes which take place during the development of epilepsy in a living animal. “If the fluorescence molecules glow, this indicates that the mouse is developing chronic epileptic seizures,” says the molecular biologist Prof. Dr. Susanne Schoch.
“About one-third of patients with temporal lobe epilepsy do not respond to medications. Our research is therefore increasingly focusing on new therapeutic options that have few side effects,” states Prof. Becker. If the zinc ions or the transcription factor MTF1 were specifically inhibited in the brain, it is possible that the development of a seizure disorder could be prevented. “However, this still needs to be demonstrated in further studies,” says Dr. Karen M.J. van Loo.
http://www3.uni-bonn.de/Press-releases/researchers-discover-an-epilepsy-switch
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