New discoveries in epileptic seizure prevention-ScienceDaily

Temporal lobe epileptic seizures are debilitating and can cause permanent damage to the patient, including nerve cell death and loss of nerve function.

Sanjay Kumar, an associate professor of biomedical science at the School of Medicine, and his team are paving the way for finding effective treatments for the disease.

The research team discovered in the brain the mechanism that triggers epileptic seizures. Their research shows that an amino acid known as D-serine works with a mechanism that helps prevent epileptic seizures, which in turn can also prevent the death of nerve cells associated with them.

The team’s findings were published in the journal Nature Communications..

The temporal lobe processes sensory information, creates memory, understands language, and controls emotions. Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy and is not ameliorated by current antiepileptic drugs.

“TLE is characterized by the loss of a fragile neuronal population in a specific brain region called the entorhinal region,” Kumar said. “I’m trying to understand why neurons die in this area of ​​the brain in the first place. Is there anything I can do to prevent these neurons from dying? That’s a very basic question.”

To better understand the pathophysiology of TLE, Kumar Labs is studying the underlying receptors in the brain. Receptors are proteins located in the gaps or junctions between two or more communication neurons. They transform signals between neurons and help them communicate.

Kumar and his team have discovered a new type of receptor in the entorhinal cortex of the brain that is informally named the “FSU receptor.” FSU receptors are potential targets for TLE therapy.

“The amazing thing about this receptor is its high calcium permeability, which we believe underlies hyperexcitability and neuronal damage in this area,” Kumar said.

Patients with TLE experience epileptic seizures because when FSU receptors invade neurons with excess calcium, the neurons are overstimulated from the influx. Overstimulation, or hyperexcitability, is the cause of death in neurons, a process known as excitotoxicity.

The researchers also found that the amino acid D-serine blocks these receptors, preventing excessive levels of calcium from reaching neurons, thereby preventing seizure activity and neuronal death.

“The uniqueness of D-serine is that, unlike other drugs, D-serine is made by the brain itself, so it is well tolerated by the brain,” Kumar said. “Many drugs that treat TLE are not well tolerated, but given that they are made in the brain, it works very well.”

The research team, with the support of Michael Roper’s lab in the Department of FSU Biochemistry, discovered that epileptic animals had reduced D-serine levels. This indicates that TLE patients may not produce D-serine as it should.

“The loss of D-serine essentially removes the brakes on these neurons and makes them hyperexcited,” Kumar said. “Next, calcium enters and causes excitotoxicity, which is why neurons die. Therefore, when braked, giving D-serine does not cause neuron loss.”

Kumar’s research points to neuroinflammation as a cause of decreased D-serine levels in the entorhinal cortex of the brain. Although D-serine is normally produced by glial cells, the neuroinflammation experienced as part of TLE can cause cellular and molecular changes in the brain that prevent it from being produced.

The next step in exploring D-serine as a viable treatment is to explore potential dosing techniques.

“We must find a creative way to administer D-serine to that particular area of ​​the human brain,” Kumar said. “The challenge is to get it to the right place. For example, we need to find out what effect it has when applied topically to that area of ​​the brain compared to systemic administration by intravenous administration. “

TLE often results from damage such as concussion and other traumatic brain injuries. D-serine has been shown to help prevent the secondary effects of such injuries when administered to the appropriate area.

“The idea of ​​an aerial pie type is a fictitious scenario of using a nebulizer, inhaling D-serine, playing soccer. Even if you experience a concussion, D can cause neuron loss. No.-Serine provides a kind of cushion in case of traumatic brain injury that can lead to the loss of neurons in the temporal lobe, “Kumaar said.

“There are some very interesting questions to ask and solve,” he added. “Importantly, we have outlined the basic bread and butter mechanisms that make D-serine work. We have established the discovery of receptors, antagonists of these receptors (D). -The discovery of serine). How it works and how to prevent the appearance of TLE. Mechanisms and pathophysiology are as relevant to animal models as humans, and there is excitement there. “