Article found on MedicalXpress
Calorie restriction has long been associated with reduced seizures in epilepsy. New research from Boston Children’s Hospital helps explain how fasting affects neurons in the brain and could lead the way to new approaches that would avoid the need for fasting or restrictive diets. The findings were published August 30 in the journal Cell Reports.
“This study is the first step in understanding how dietary therapies for epilepsy work,” says first author Christopher J. Yuskaitis, MD, Ph.D., a neurologist with the Epilepsy Center and Epilepsy Genetics Program at Boston Children’s Hospital. “The mechanisms have until now been completely unknown.”
DEPDC5, mTOR, and fasting
To connect the dots between diet and seizures, the researchers began with existing knowledge. They knew that the well-known mTOR cellular pathway is involved in many neurological disorders and had shown previously that over-activation of this pathway in neurons increases susceptibility to seizures. Studies by others had shown that mTORC activity is inhibited by acute fasting, though these studies didn’t look at the brain.
In the new study, they showed in a mouse seizure model that mTOR signaling was reduced in the brain after fasting. Additional studies of cultured rat neurons in a dish suggest that this fasting effect is primarily driven by the lack of three amino acids (leucine, arginine, and glutamine).
Going further, the team demonstrated that the presence of these nutrients is sensed by the DEPDC5 protein. When they knocked out DEPDC5 in the brain, mTOR activity was not reduced and fasting no longer protected the mice against seizures.