Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Boosting key protein in brain could improve seizure treatment

17.08.2006
A naturally occurring protein in our brains could be the basis for a more promising epilepsy treatment - without the nasty side effects caused by many of the current medications.

Researchers at the Stanford University School of Medicine discovered that the drug valproic acid boosts the amount of the protein neuropeptide Y in the brain by about 50 percent. What's more, they found that the drug increased the protein in only two parts of the brain - the thalamus and hippocampus, areas associated respectively with petit mal and temporal lobe epileptic seizures. The neuropeptide Y levels in other parts of the brain were unaffected. "That was quite a surprise," said Julia Brill, a postdoctoral scholar in Stanford's neurology department who worked on the study.

VPA has long been a mainstay in treating epilepsy, although how it suppressed seizures was a mystery. It has a minimal sedative effect, but a host of other unpleasant side effects including weight gain, hair loss, upset stomach and liver problems, as well as causing birth defects if taken by pregnant women, so it's less than an ideal medication.

But discovering that VPA triggers an increase in neuropeptide Y not only helps explain how VPA works, it suggests a possible way to stimulate the brain to quell seizures: The key could be to increase the amount of this anti-epileptic compound in the brain. Neuropeptides are very small proteins that often help transmit signals between neurons, the specialized cells in the brain that generate and transmit thought.

"This finding really emphasizes that our brains have the inherent capacity to stop seizures," said John Huguenard, PhD, associate professor of neurology and neurological sciences and senior author of a paper describing the work published in June in the Journal of Neuroscience, on which Brill is first author. Although there may be more than one mechanism by which our brains stop seizures, an increase in neuropeptide Y is clearly one of them, he said, and he and Brill are already exploring other ways to trigger production of the peptide and prolong its action.

The precise nature of this response to VPA, which is sold under the brand name Depakote, offers the promise of a new approach in treating seizures.

Unlike VPA, most anti-epileptic medications work by binding to various channels or receptors on neurons throughout the brain, thereby directly slowing the pace of signal transmission and reception. This approach to treating epilepsy is effective because seizures occur when neurons are overstimulated and begin firing too rapidly and in unison, sending pulsing barrages of signals coursing through the brain. Slowing the pace of communication among the neurons prevents them from becoming overstimulated.

But a seizure often originates in just one part of the brain, so preventing seizures by slowing down the entire brain is like trying to stop cars from speeding on one particular thoroughfare by installing speed bumps on every street in town.

Huguenard and Brill said that if a way could be found to increase neuropeptide Y only in the part of the brain from which a particular type of seizure emanates, it might be possible to develop anti-epileptic medications with few, if any, side effects.

Robert Fisher, MD, professor of neurology and neurological sciences at Stanford and a practicing clinician who treats epileptic patients, said the findings point to a potentially better way of treating the disease. Fisher was not involved in this study, though he has worked with Huguenard on other research.

"All of our seizure medications are controlled poisons, all with significant side effects," Fisher explained. "If we can find out more about the natural mechanisms that produce seizures, then we can hopefully counteract it with a rifle bullet rather than a shotgun that causes all kinds of side effects."

Brill made the discovery about VPA while working with rats. Increases of neuropeptide Y had been observed in rodent brains in response to seizures, and injections of the peptide had been shown to suppress seizures in the animals. So Brill and Huguenard suspected VPA might work by somehow acting to increase the neuropeptide Y levels.

When humans are treated with VPA, they typically receive increasing doses over a period of days before it takes effect, so Brill set up a comparable regimen with some rats. After giving them doses of VPA in concentrations known to be large enough to suppress seizures, she examined their brains and discovered the localized increases in the peptide. She also determined that after receiving the VPA, both the duration of the seizures and the extent to which they spread from their site of origin were reduced. With epileptic seizures, an initially small seizure can spread to other parts of the brain and trigger more severe seizures.

VPA is primarily used to treat absence epilepsy seizures, which mainly affect children. These are seizures that involve the thalamus, in which the sufferer appears to simply freeze for a few moments or up to half a minute. Although such seizures might appear minor, in fact they can happen dozens of times a day and have a severe effect on the ability of children to lead normal lives.

Exactly how VPA triggers the increased production of neuropeptide Y in the thalamus and hippocampus is still a puzzle.

Brill said there are probably intermediate steps, a cascade of signals, leading to the boost in the neuropeptide. "If you can identify the pathway that valproic acid uses to increase the neuropeptide Y, then maybe you can figure out a different way to stimulate that same pathway and get neuropeptide Y production," she said, adding that if a way could be found to activate the signals closer to the final stage that triggers the peptide increase, "maybe you could get rid of some of the detrimental effects that valproic acid has."

"Our next step will be to understand the signaling pathways that lead to the targeted increase in NPY in the different brain regions," Huguenard added.

Louis Bergeron | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>