College of Medicine

A team of Florida State University College of Medicine researchers has established a correlation between a specific protein in the brain and increased vulnerability to neurodegeneration in temporal lobe epilepsy (TLE).

TLE is the most common form of epilepsy in adults and is often resistant to medication.

The findings are published in the Journal of Neurophysiology.

Professor of Biomedical Sciences Sanjay Kumar, who led the study, said the team used a novel technique that made it possible to study small amounts of tissue from hard-to-reach regions within the brain. Kumar, FSU research faculty Stephen Beesley and then-doctoral student Thomas Sullenberger focused on a chemical messenger called Glutamate  and one of its receptors, N-methyl-D-aspartate (NMDA). Glutamate plays a major role in learning and memory, and it must be present in the right concentration at the right time for the brain to function properly.

Glutamate is also the body’s most abundant amino acid, a building block of protein.

The team discovered that while two proteins commonly associated with NMDA – GluN1 and GluN2 – were evenly distributed in a critical hippocampal region of the brain, a third one – GluN3 – was distributed on a gradient. A pattern of neuron loss in the hippocampal and para-hippocampal regions of the brain is a hallmark feature of the disease.

Because GluN3 makes neurons more susceptible to calcium-induced cellular damage, the discovery helps researchers narrow the focus to identify exactly where neurons are dying and in how large an area.

Kumar has applied to patent the novel technique, known as area-specific tissue analysis (ASTA), that he developed for making this type of research more efficient. ASTA’s added precision created an improved method of testing for both the presence and volume of specific proteins linked to TLE.

Ultimately, Kumar said, discovering the gradient distribution of GluN3 will allow researchers to access more relevant tissue samples.

The Kumar Lab focuses on deciphering the basic mechanisms underlying TLE, as well as identifying and isolating vulnerable cells and circuits within the hippocampal region to promote the discovery of more effective therapies and interventions.

The work is supported in part by a grant from the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health.

Contact Audrey Post at audrey.post@med.fsu.edu