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?"
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—they quiet the nerve system down."
When dosed with NBD-steroid, nerve cells still responded to stimuli as readily as they had prior to exposure. Just to see where the modified steroid was going, though, researchers exposed the cells to light.
"All of a sudden, the response to the steroid was back, and the nerve cells were more reluctant to react to stimuli," Mennerick says. "And we knew we had found something very interesting."
To confirm what was happening, scientists dosed two of a nerve cell's many different branches with NBD-steroid. When they shone a light on one of the branches, its readiness to respond decreased, while the readiness of the branch not exposed to light remained the same.
Department of Anesthesiology colleagues tested the compound's effects on tadpoles.
"Tadpoles rapidly take up drugs through their skin, so they're frequently used to test potential anesthetics," Mennerick notes. "And of course, given that it's a photoactive drug, they make a nice test subject because they're mostly translucent."
Tadpoles swimming in a solution of NBD-steroid went to sleep at the bottom of their beaker when exposed to light.
Mennerick and his colleagues are currently seeking to identify or create an animal model of epilepsy that lets them test the NBD-steroid's potential as a therapeutic.
They are also looking for a new fluorescent tag that responds to longer wavelengths of light. Unlike many photoactive compounds, the NBD-steroid responds not to ultraviolet light but to light from the blue region of the electromagnetic spectrum. This helps because the longer wavelengths of blue light penetrate farther into tissue than ultraviolet light and are less damaging to it. Molecules that fluoresce in response to even longer wavelengths of light are available, and scientists are testing whether any of them can create the same effect when bound to the steroid.
Michael C. Purdy | EurekAlert!
Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research