Restricting calories has long been associated with fewer episodes of seizures in epileptic patients. The effects of fasting on brain neurons are now better understood according to a recent study from Boston Children′s Hospital published in the journal Cell Reports.

The mTOR cellular pathway plays a vital role in various neurological illnesses. Studies have previously demonstrated that over-activating this route in neurons makes them more susceptible to seizures. Also, it is known that the DEPDC5 protein′s signaling inhibits the mTOR pathway. Recent research revealed that DEPDC5 mutations were common in epilepsy patients, suggesting a connection between these conditions and sudden infant death syndrome, focal epilepsy, and infantile spasms.

In the current work, the researchers used a mouse seizure model and demonstrated that mTOR signaling was decreased in the brain after fasting. Additional research on rat neurons grown in culture suggests that the absence of three amino acids (leucine, arginine, and glutamine) causes this fasting effect. It also showed how the DEPDC5 protein detects 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.

Therefore, scientists suggest that patients with DEPDC5 mutations may not benefit from dietary modification because they cannot perceive the loss of amino acids. However, patients without DEPDC5 mutations might gain from a focused nutritional approach.

The study team is currently testing particular 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. Such research might potentially offer a fresh perspective on all neurologic illnesses.  (The Print, 9 September, 2022)