Research on the impact of fasting on brain neurons


Neurologist with an MD and PhD from Boston Children’s Hospital’s Epilepsy Center and Epilepsy Genetics Program. “The mechanics are absolutely unknown as of right now.”

DEPDC5, mTOR, and fasting

The researchers started with the body of knowledge 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 recently 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 knocks out DEPDC5 in the brain, says Yuskaitis. That inspired us to investigate the relationship between DEPDC5, mTOR, and fasting.

Amino acid sensing

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 suggests that patients with DEPDC5 mutations may not benefit from dietary modification because they are unable to sense the loss of amino acids. However, patients without DEPDC5 mutations might 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 specific 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 therapies other than the ketogenic diet, which can be challenging to follow for a long time due to side effects.”

Such research might potentially offer a fresh perspective on all neurologic illnesses.

According to senior researcher Mustafa Sahin, MD, PhD, managing director of the Rosamund Stone Zander Translational Neuroscience Center at Boston Children’s, “We are starting to gain fundamental insights into the role of nutrients in brain function using these rare genetic disorders.” Findings from these uncommon illnesses may pave the way for more effective treatments for epilepsy generally.