Light-activated compound silences nerves, may one day help epileptics

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Brain activity has been compared to a light bulb turning on in the head. Scientists at Washington University School of Medicine in St. Louis have reversed this notion, creating a drug that stops brain activity when a light shines on it.

The unexpected result, reported online in Nature Neuroscience, turned several lights on in researchers' heads.

"This is daydreaming at this point, but we might one day combine this drug with a small implanted light to stop seizures," says senior author Steven Mennerick, Ph.D. associate professor of psychiatry and of anatomy and neurobiology. "Some current experimental epilepsy treatments involve the implanting of an electrode, so why not a light?"

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The new compound activates the same receptor used by many anesthetics and tranquilizers, making it harder for a brain cell to respond to stimulation. Mennerick and colleagues including lead author Larry Eisenman, M.D., Ph.D., assistant professor of neurology, tested the drug on cells in culture set up to behave like they were involved in a seizure, with the cells rapidly and repeatedly firing. When they added the new drug and shone a light on the cells, the seizure-like firing pattern calmed.

If the drug is adapted for epilepsy, Mennerick notes, it is most likely to help in cases where seizures consistently originate from the same brain region. Theoretically, doctors could keep a patient on regular doses of the new drug and implant a small fiber optic light in the dysfunctional region. The light would activate the drug only when seizure-like firing patterns started to appear.

Scientists in the laboratory of Douglas F. Covey, Ph.D., professor of molecular biology and pharmacology, created the drug by linking a steroid known to have anesthetic effects with a molecule, known as NBD, that fluoresces in response to blue light. Mennerick and colleagues were hoping to use the new compound, which they call the NBD-steroid, to trace the steroid's path in the nervous system.

To their initial disappointment, the researchers found that adding the fluorescent tag to the steroid had disabled it.

"Normally, the steroid keeps the cell quiet in the face of stimuli that would otherwise cause it to fire," Mennerick says. "That's why drugs like barbiturates and Valium, which act on the same receptor as the steroid, are sedatives

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