Molecular Brain Changes in Epileptic Animals Explains Stress-Induced Seizures

Molecular Brain Changes in Epileptic Animals Explains Stress-Induced Seizures

Epilepsy changes how the brain reacts to stress – a research proven fact that explains why patients with epilepsy who experience stress and anxiety often end up in worse condition and with more seizures.

The finding, from a study led by Michael O. Poulter and research team at the University of Western Ontario, opens up possibilities for developing drugs to prevent stress-induced seizures in epileptic patients.

The study, “A switch in G protein coupling for type 1 corticotropin-releasing factor receptors promotes excitability in epileptic brains,” was published in Science Signaling.

For the study, Poulter and team focused on a molecule called corticotropin-releasing factor, or CRF. In the brain, the molecule is crucial for coordinating stress responses.

In a healthy state, CRF reduces the activity of a brain area called the piriform cortex, a region scientists know is involved in seizure activity in humans. Using a rat model of epilepsy, the university researchers demonstrated that, in contrast to its soothing effect in a healthy brain, CRF released in the epileptic brain made things worse by increasing activity in the piriform cortex.

“When we used CRF on the epileptic brain, the polarity of the effect flipped; it went from inhibiting the piriform cortex to exciting it,” Poulter said. “At that point we became excited, and decided to explore exactly why this was happening.”

The team found in the epileptic brain of the rats, that CRF binding to its receptor triggered an entirely different signaling pathway inside the cell that it would in a healthy brain. In this way, a stress response intended to be beneficial, instead became an epileptic trigger.

According to the study: “What we found is that there is a switch in the molecular signaling in the brain. In the model of epilepsy, the CRF switches from signaling through one cascade to one that’s completely different and we discovered that the catalyst for that is a protein in the brain called regulator of G protein signaling protein type 2.”

Such a clear-cut effect opens up possibility that drugs designed to block CRF signaling could prevent stress-triggered epileptic seizures.

“We are very excited about this possibility for treating epilepsy patients,” Poulter said.

The study shows the potential for possible research and drug development for other brain diseases and conditions including depression or schizophrenia that could be worsened by stress.

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