Scientists solve century-old neuroscience mystery; answers may lead to epilepsy treatment
Scientists at the Virginia Tech Carilion Research Institute have solved a 125-year-old mystery of the brain, and, in the process, uncovered a potential treatment for acquired epilepsy. The School of Neuroscience is very proud to publish this great accomplishment of a research team led by our director, Harald Sontheimer.
Since 1893, scientists have known about enigmatic structures called perineuronal nets wrapped around neurons, but the function of the nets remained elusive.
Now, a research team led by Harald Sontheimer, the director of the VTCRI Center for Glial Biology in Health, Disease, and Cancer and the executive director of the School of Neuroscience, part of the Virginia Tech College of Science, has determined the nets modulate electrical impulses in the brain. What’s more, brain seizures can occur if the nets are dissolved.
The discovery, published Friday, Nov. 9 in Nature Communications, has implications in various forms of acquired epilepsy, a type of seizure disorder that results from brain lesions caused by trauma, infection, or tumors in the brain.
“We started by investigating tumor-associated epilepsy, and we accidentally learned something else important about how the brain works in disease and in health,” Sontheimer said.
The researchers initially made their finding in a mouse model of epilepsy caused by the deadly brain cancer known as glioblastoma, the first symptom of which is often a seizure.
Glioblastoma is the only cancer whose growth is restricted by space. Since the skull blocks the cancer from expanding outward, the tumor produces an excitatory chemical neurotransmitter called glutamate in excessive amounts that kills neighboring healthy cells to make room to grow.
The researchers saw that glutamate targeted brain cells, producing a different chemical neurotransmitter called “GABA,” that usually calms neurons by inhibiting them from firing electrical impulses once the messages are relayed. Without GABA, the brain becomes too excited and can seize.
In addition to glutamate, the tumor also secretes an enzyme aimed at destroying the surrounding extracellular matrix, a gel-like substance that holds brain cells in place. Glioblastomas are highly malignant and notoriously invasive – the enzyme is the knife that cuts the cancer’s tethers and lets it migrate freely.
“Unexpectedly, we also saw the enzyme attacking the perineuronal nets,” Sontheimer said, noting that the nets are primarily found wrapped around the GABA-secreting inhibitory neurons, which help prevent seizures. “It was a surprise to see this bystander effect of seizure activity once the neurons were stripped of their nets.”