The University of California, Irvine and French scientists have discovered the switch that causes healthy brain cells to become epileptic. This breakthrough may help treat and prevent the most common form of epilepsy, temporal lobe epilepsy (TLE).
Epilepsy is a common neurological disorder that is characterized by seizures. Temporal lobe epilepsy is a type of epilepsy where the seizures arise from one or both of the temporal lobes of the brain. It affects one to two percent of the population and is currently resistant to treatment 30% of the time.
Dr. Tallie Z. Baram, of UC Irvine, discovered that TLE occurs after major reorganization of the molecules governing the behavior of neurons. This reorganization often stems from febrile seizures, brain infections, or trauma.
“This discovery marks a dramatic change in our understanding of how TLE comes about. Previously, it was believed that neurons died after damaging events and that the remaining neurons reorganized with abnormal connections,” said Baram, the Danette Shepard Chair in Neurological Studies. “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.”
Joining forces with French scientists from the University of Marseille, Dr. Baram and the UC Irvine researchers, began investigation of the reason for this abnormal behavior by focusing on ion channels.
In particular, they looked at the ion channel HCN1, hoping to find the trigger of previously healthy brain cells becoming epileptic ones. This channel is often suppressed during epileptic seizures.
The scientists discovered that the HCN1 gene, along with dozens of others, is altered by a major cellular repressor called NRSF.
NRSF proteins work by attaching themselves to DNA on certain genes and shutting them down. This causes the neurons to fire abnormally triggering the development of epilepsy. When the researchers prevented NRSF from attaching to HCN1, they found that epilepsy was markedly lessened.
“We’re quite excited about this discovery,” Baram said. “Understanding how previous brain infections, seizures or injuries can interact with the cellular machinery to cause epilepsy is a crucial step toward designing drugs to prevent the process. We don’t want to just treat people with epilepsy. We hope to develop medicines that will prevent epilepsy from occurring – and influence the lives of millions of people around the globe.”
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