Restricting calories has long been associated with fewer seizures in epileptics. The effects of fasting on brain neurons are now better understood according to recent study from Boston Children’s Hospital, which may also open the way for novel therapies that don’t include fasting or stringent diets.
The journal Cell Reports reported the study’s findings. According to first author Christopher J. Yuskaitis, MD, PhD, a neurologist from the Epilepsy Center and Epilepsy Genetics Program at Boston Children’s Hospital, “this study represents the first step in understanding how dietary therapy for epilepsy work.” “The mechanics are absolutely unknown as of right moment.”
Fasting, DEPDC5 and mTOR
The researchers started with the body of evidence that already existed to link food and seizures. They were aware that many neurological illnesses include the well-known mTOR cellular pathway, and they had previously demonstrated that over-activating this system in neurons makes them more susceptible to seizures. While these investigations didn’t focus on the brain, they did demonstrate that acute fasting inhibits mTORC function.
Finally, Yuskaitis and associates became aware that the DEPDC5 protein’s signalling inhibits the mTOR pathway. That was noteworthy because a lot of epileptics have lately had mutations in the DEPDC5 gene. Children’s abrupt death, infantile spasms, and focal epilepsy have all been connected to DEPDC5 mutations.
We discovered that employing a mTOR inhibitor helped lower seizures when we employed an animal model that precisely wipes off DEPDC5 in the brain, says Yuskaitis. That inspired us to investigate the relationship between DEPDC5, mTOR, and fasting.
Sensing of amino acids
In the recent work, it was demonstrated that mTOR signalling was decreased in the brain after fasting using a mouse seizure model. Additional research on rat neurons grown in culture suggests that the absence of three amino acids is what causes this fasting effect (leucine, arginine, and glutamine).
Further, the group showed that the DEPDC5 protein can detect the presence of these nutrients. When DEPDC5 was removed from the brain, mTOR activity was unaffected, and fasting no longer prevented seizures in the mice.
According to Yuskaitis, amino acid sensing appears to be essential for the positive benefits of fasting on seizures. “This shows that individuals with DEPDC5 mutations may not benefit from dietary modification because they are unable to feel the loss of amino acids. However, individuals without DEPDC5 mutations could gain from a focused nutritional approach.”
According to him, this may be accomplished by consuming meals that are lower in the three amino acids or by using drugs or supplements that prevent the absorption of those amino acids.
Following a ketogenic diet
This research is simply the beginning. Yuskaitis and associates are currently interested in testing certain amino acid-free diets on animal models to see how they affect seizure frequency. They also aim to investigate how the ketogenic diet, a well-known method of treating epilepsy, reduces seizure frequency. Nobody now understands why this high-fat, low-carb diet is effective.
According to Yuskaitis, “We’re hoping this will help us identify new dietary-based treatments other than the ketogenic diet, which may be challenging to maintain for a long time owing to side effects.”
Such research could potentially offer a fresh perspective on all neurologic illnesses.
According to prominent researcher Mustafa Sahin, MD, PhD, executive director of the Rosamund Stone Zander Translational Neuroscience Center at Boston Children’s, “We are starting to get basic insights into the role of nutrition in brain function using these uncommon genetic illnesses.” Findings from these uncommon illnesses may pave the way for more effective therapies for epilepsy generally.