Video: Explains in more detail the different receptors affected by epilepsy.
Researchers at the University of Copenhagen were able to pinpoint specific subtypes of nerve cells and neural circuits affected by epilepsy. Epilepsy is highly variable between individuals and the severity of their case, so understanding exactly which neurons are malfunctioning is critical to successfully treating epilepsy patients of all kinds.
Until now, sequencing technology only allowed for studying the expression of genes in whole layers of the brain, which include many different types and subtypes of neurons. The imprecise technology and variability across patients turned up few commonly affected genes. Therefore, even a cocktail of treatment options does not target a patient's specific problem, leaving 30-40% of severely epileptic patients to experience seizures still.
The Khodosevich laboratory in Copenhagen employed single-nuclei RNA sequencing (snRNA-Seq) to identify specific points of overexcitation in neural circuits. The researchers found that in the temporal cortex alone, more than 60 subtypes of neurons and more than 20,000 genes were dysregulated in some way and contribute to seizures. Most of these genes have not been linked to epilepsy before because they are not common to all, or even most, cases.
For example, in just the fifth and sixth layers of the epileptic cortex, the researchers found various dysregulated genes, the effects of which fuel the severity of one another. For example, GLUR1 is upregulated, which is thought to increase the excitability of neurons. Simultaneously, GLUR2 is downregulated, which allows more calcium to flow, interrupting cell signaling and compounding the severity of a seizure caused by the upregulation of GLUR1.
The snRNA-Seq method suspends individual neurons in droplets, keeping them intact, unlike traditional methods that use enzymes to force cells' separation. Neurons are too delicate for the enzymatic methods, and therefore could not be sequenced on a single-celled basis until now.
Future studies will continue to look at the effect of specific types and subtypes of neurons to determine which pathways are major drivers of seizures and which agitate the condition. The goal is to use this precise understanding of epilepsy to improve the effectiveness of treatment.