The idea of fasting has been implemented for years in people with epilepsy as a way of reducing seizure activity. But the molecular mechanisms involved have baffled scientists until a recent study.
The study proved to be a primary one in further determining how such dietary changes in epilepsy actually work. The answers could prove to open up new possibilities for the treatment of epilepsy.
Scientists at Boston Children’s Hospital discovered new information to explain why fasting influences neuronal activity in the brain.
According to Dr. Christopher Yuskaitis, a neurologist with the Epilepsy Center and Epilepsy Genetics Program at Boston Children’s Hospital, scientists began looking more deeply into what they did know. That a specific molecular pathway in the brain cells called mTOR, had previously been associated with seizures. The overactivation of these networks directly correlate to increased seizure activity. While the same pathway had been shown to be inhibited by fasting.
The reason is because the signaling molecule called the DEPDC5 is what they found to inhibit the mTOR pathway.
Dr. Yuskaitis explained, “ When we used an animal model that knocks out DEPDC5 specifically in the brain, we found that we could reduce seizures by using mTOR inhibitor. That gave us the idea to explore the connection between DEPDC5, mTOR and fasting.”
The scientists used mouse seizure models to discover that the fasting effect is driven by the lack of three essential sensing amino acids- leucine, arginine and glutamine, while in a fasted brain state.
Looking further, the scientists noticed that the DEPDC5 signaling molecule was able to sense the three amino acids.
But they also noticed that when the signaling molecule DEPDC5 was mutated, (or it could no longer be produced in the brain of the animal, which rendered it incapable of sensing the amino acids), the seizure activity was no longer reduced because there was no beneficial impact from the fasting.
Dr. Yuskaitis explained, “ Amino acid sensing seems to be critical for the beneficial effects of fasting on seizures. This suggests that patients with DEPCD5 mutations can’t sense the loss of amino acids and may not benefit from dietary manipulation, But patients who don’t have DEPDC5 mutations may benefit from a targeted dietary strategy.” He went on to add, “ We’re hoping this will help us uncover additional dietary-based therapies other than ketogenic diet, which is sometimes difficult to follow long term due to side effects.”
I believe they now want to follow up the study with more targeted approach using other amino acids and see how they can impact seizure activity in animal studies.
For now, it appears that fasting has a critical anti seizure effect on the brain, based on the signaling molecule mechanism DEPCD5 has on the mTOR pathway.
More research should reveal promising insights which could lead to greater understanding of epilepsy. What specific mechanisms are involved and to what degree is essential in coming up with more widespread therapeutic strategies for the treatment of epilepsy.
-A Balanced Brain is a Better Brain For a Happier Life-