Central switch responsible for the transformation of healthy brain cells into epileptic brain cells has been identified by researchers.
UC Irvine neurologist and neuroscientist Dr. Tallie Z. Baram and her colleagues found that TLE manifests after a major reorganization of the molecules governing the behaviour of neurons, the cells that communicate within the brain.
These alterations often stem from prolonged febrile seizures, brain infections or trauma.
"This discovery marks a dramatic change in our understanding of how TLE comes about," Baram, the Danette Shepard Chair in Neurological Studies, said.
"Previously, it was believed that neurons died after damaging events and that the remaining neurons reorganized with abnormal connections.
"However, in both people and model animals, epilepsy can arise without the apparent death of brain cells. The neurons simply seem to behave in a very abnormal way," Baram explained.
To learn why, Baram's UCI team collaborated with a French group led by Christophe Bernard of the University of Marseille and Inserm.
They focused on ion channels, molecules that straddle the boundaries of brain cells and govern how they fire and communicate among themselves.
Specifically, they explored an ion channel called HCN1, which is suppressed in response to brain seizures, injuries and infections that lead to epilepsy, hoping to find the long-sought mechanism that triggers epileptic activity in previously normal brain cells.
In their study the researchers reveal that mechanism: The HCN1 channel gene and about three dozen other important genes are altered by a major cellular repressor called NRSF, which increases after events that give rise to epilepsy.
"NRSF operates like a master switch on many genes affecting neuron function. And if its levels increase, it can provoke changes lasting for years," Shawn McClelland, UCI researcher and study co-author, said.
The findings have been published online in the Annals of Neurology.