A team of researchers from the Florida State University College of Medicine has found that an amino acid produced by the brain could play a crucial role in preventing a type of epileptic seizure.
Temporal lobe epileptic seizures are debilitating and can cause lasting damage in patients, including neuronal death and loss of neuron function.
Sanjay Kumar, an associate professor in the College of Medicine’s Department of Biomedical Sciences, and his team are paving the way toward finding effective therapies for this disease.
The research team found a mechanism in the brain responsible for triggering epileptic seizures. Their research indicates that an amino acid known as D-serine could work with the mechanism to help prevent epileptic seizures, thereby also preventing the death of neural cells that accompanies them.
The team’s findings were published in the journal Nature Communications.
The temporal lobe processes sensory information and creates memories, comprehends language and controls emotions. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is not improved with current anti-epileptic medications.
“A hallmark of TLE is the loss of a vulnerable population of neurons in a particular brain region called the entorhinal area,” Kumar said. “We’re trying to understand why neurons die in this brain region in the first place. From there, is there anything that we can do to stop these neurons from dying? It’s a very fundamental question.”
To help further understand TLE pathophysiology, the Kumar lab studies underlying receptors in the brain. Receptors are proteins located in the gaps, or junctions, between two or more communicating neurons. They convert signals between the neurons, aiding in their communication.
Kumar and his team discovered a new type of receptor that they informally named the “FSU receptor” in the entorhinal cortex of the brain. The FSU receptor is a potential target for TLE therapy.
“What’s striking about this receptor is that it is highly calcium-permeable, which is what we believe underlies the hyperexcitability and the damage to neurons in this region,” Kumar said.
When FSU receptors allow too much calcium to enter neurons, TLE patients experience epileptic seizures as neurons become overstimulated from the influx. The overstimulation, or hyperexcitability, is what causes neurons to die, a process known as excitotoxicity.
The research team also found that the amino acid D-serine blocks these receptors to prevent excess levels of calcium from reaching neurons, thereby preventing seizure activity and neuronal death.
“What’s unique about D-serine, unlike any other drugs that are out there, is that D-serine is made in the brain itself, so it’s well-tolerated by the brain,” Kumar said. “Many medications that deal with treating TLE are not well-tolerated, but given that this is made in the brain, it works very well.”
With assistance from Michael Roper’s lab in the FSU Department of Chemistry and Biochemistry, the research team found that D-serine levels were depleted