“Amino acid sensing seems to be critical for the beneficial effects of fasting on seizures,” says Yuskaitis. When they used genetic techniques to eliminate DEPDC5 in the brain, mTOR activity was not reduced and fasting no longer protected the mice against seizures. In additional studies of rat neurons, they found that the lack of three amino acids (leucine, arginine, and glutamine) during fasting accounted for most of fasting’s effects on mTOR signaling.įinally, the team showed that the presence of these amino acids is sensed by the DEPDC5 protein. In the new study, the researchers showed that when seizure-prone mice fasted for 24 hours, mTOR signaling in their brains was reduced. “That gave us the idea to explore the connection between DEPDC5, mTOR, and fasting.” Amino acid sensing “When we used an animal model that knocks out DEPDC5 specifically in the brain, we found that we could reduce seizures by using an mTOR inhibitor,” says Yuskaitis. Intriguingly, mutations in the DEPDC5 gene have recently been linked to epilepsy, including focal epilepsy, infantile spasms, and sudden unexplained death in children. The mechanisms until now have been completely unknown.”įinally, Yuskaitis and colleagues knew that a protein called DEPDC5 acts as a brake on the mTOR pathway. This study is the first step in understanding how dietary therapies for epilepsy work. Studies by others had shown that fasting inhibits mTOR activity, though these studies didn’t look at the brain.
In a previous study, they had shown that over-activation of this pathway in neurons increases susceptibility to seizures. The researchers already knew that a cellular pathway known as the mTOR pathway is involved in many neurological disorders. “The mechanisms have until now been completely unknown.” Connecting the dots between diet and seizures Yuskaitis, MD, PhD, a neurologist with the Epilepsy Center and Epilepsy Genetics Program at Boston Children’s Hospital. “This study is the first step in understanding how dietary therapies for epilepsy work,” says first author Christopher J. The findings could lead the way to new approaches that would avoid the need for fasting or even the ketogenic diet, which mimics some of the effects of fasting and is now sometimes used to treat epilepsy. New research from Boston Children’s helps explain how fasting affects the brain at the molecular level. But the reasons have remained mysterious. Illustration: Sebastian Stankiewicz/Boston Children’s Hospital)įasting has been believed since ancient times to curb seizures in epilepsy, and small patient studies in the early 1900s have revived the idea. Why? New research helps connect the dots and could yield new treatments that don’t involve fasting. Since ancient times, fasting has been seen as a way to limit seizures.
0 kommentar(er)
