Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Boosting key protein in brain could improve seizure treatment

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:

More articles from Life Sciences:

nachricht International team discovers novel Alzheimer's disease risk gene among Icelanders
24.10.2016 | Baylor College of Medicine

nachricht New bacteria groups, and stunning diversity, discovered underground
24.10.2016 | DOE/Lawrence Berkeley National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

New method increases energy density in lithium batteries

24.10.2016 | Power and Electrical Engineering

International team discovers novel Alzheimer's disease risk gene among Icelanders

24.10.2016 | Life Sciences

New bacteria groups, and stunning diversity, discovered underground

24.10.2016 | Life Sciences

More VideoLinks >>>