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Researchers discover why stress leads to increased seizures in epilepsy patients

June 14, 2016

For epilepsy patients, stress and anxiety can exacerbate their condition; increasing the frequency and severity of seizures. Until now, it was unclear why this happened and what could be done to prevent it.

In a study published today in the journal Science Signaling, researchers at Western University have shown that epilepsy actually changes the way the brain reacts to stress, and have used these findings to point to new drugs that may prevent stress-induced seizures.

Michael O. Poulter, PhD, Professor in the Department of Physiology and Pharmacology at Western's Schulich School of Medicine & Dentistry and a Robarts Research Institute Scientist explains that the disease produces changes in neuronal signaling that increases seizure occurrence by converting a beneficial stress response into an epileptic trigger.

Poulter and his team, including PhD candidate and first author Chakravarthi Narla, studied a neurotransmitter called corticotropin-releasing factor (CRF) that coordinates many behavioural responses to stress in the central nervous system. Using a rat-model of epilepsy, they examined the effect of this neurotransmitter on the piriform cortex, a region of the brain that easily supports seizures in humans.

They found that in a normal brain, CRF diminished the activity of this seizure-producing part of the brain, but in the diseased brain, it did the exact opposite - ramping up the activity of the piriform cortex instead.

"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."

"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 (RGS2)."

The research points to the possibility that CRF-blocking drugs would prevent stress-induced seizures in epileptic patients.

"We are very excited about this possibility for treating epilepsy patients," said Poulter. The broader implications are that brain diseases may induce changes in other neurochemical processes that make disorders like depression or schizophrenia worse than they might otherwise be.
-end-
MEDIA CONTACT: Crystal Mackay, Media Relations Officer, Schulich School of Medicine & Dentistry, Western University, t. 519.661.2111 ext. 80387, c. 519.933.5944, crystal.mackay@schulich.uwo.ca @CrystalMackay

ABOUT WESTERN

Western University delivers an academic experience second to none. Since 1878, The Western Experience has combined academic excellence with life-long opportunities for intellectual, social and cultural growth in order to better serve our communities. Our research excellence expands knowledge and drives discovery with real-world application. Western attracts individuals with a broad worldview, seeking to study, influence and lead in the international community.

ABOUT THE SCHULICH SCHOOL OF MEDICINE & DENTISTRY

The Schulich School of Medicine & Dentistry at Western University is one of Canada's preeminent medical and dental schools. Established in 1881, it was one of the founding schools of Western University and is known for being the birthplace of family medicine in Canada. For more than 130 years, the School has demonstrated a commitment to academic excellence and a passion for scientific discovery.

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