Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Study may explain how a well-known epilepsy and pain drug works

A Duke University Medical Center researcher who spent years looking for the signals that prompt the brain to form new connections between neurons has found one that may explain precisely how a well-known drug for epilepsy and pain actually works.

The finding may also point to new therapies for brain injury and neuropathic pain.

The role of neurons in the brain and nervous system is well known, but astrocytes, a different type of brain cell, still are largely a mystery. Duke scientist Cagla Eroglu, Ph.D. has discovered a receptor that receives messages from astrocytes so that the brain can form excitatory synapses, the cell-to-cell connections that can become overactive in conditions such as epilepsy. Working with a team of scientists from other institutions, Eroglu found this receptor is also blocked by the anti-convulsant drug gabapentin (Neurontin™).

The study will appear in the Oct. 16 issue of Cell.

"The study links astrocytes and their role in synapse formation to diseases, so if the normal process goes wrong, this may explain why people get epilepsy, why epilepsy gets worse, or why they have neuropathic pain," said Eroglu, assistant professor in the Duke Department of Cell Biology. "It's a fine balance, because synapse formation has to occur during development for neurons to transmit brain signals, but if this happens in an uncontrolled manner in the adult brain, it could lead to these debilitating conditions."

Eroglu spent years looking for this neuronal receptor, which prompts synapse formation. "The key clue came when we chopped thrombospondin, a protein that comes from astrocytes and triggers establishment of synapses, into small fragments and put it onto neurons. We found that a specific portion of thrombospondin, the EGF-like domain, was equally effective as the whole protein. This gave me the clue that was necessary to identify its neuronal receptor. However it took me a while to do so."

On advice she heard from a lecture by another scientist, Nobel laureate Linda Buck – "Spend more time thinking about your experiments and your results before designing new experiments" – Eroglu took a short break from her bench-work, went home, and reasoned her way through several possibilities, finally settling on the idea that a receptor for the molecule gabapentin might be a key to regulating the formation of synapses. Excited, she returned to the lab and verified the interaction between proteins. "When I discovered that gabapentin completely blocked synapse formation between isolated neurons, I could not sleep for days until I replicated the results."

The research also points to the need for further research on gabapentin's actions, Eroglu said. The drug gabapentin strongly blocks the receptor, reducing synapse formation in rodents.

"The question is whether gabapentin might be linked with or interfere with cognitive ability, especially in the developing fetus of a woman taking the drug to control epilepsy," Ergolu said. "But of course this needs to be balanced with the mother's need to prevent her from having seizures."

"Likewise, while it is rare that a young child is given gabapentin for seizures, I think scientists need to study whether this possibly could be linked with side effects of this drug in children such as hyperactivity, irritability and maybe even cognitive problems," she said.

Gabapentin may also be a boon for certain conditions that haven't yet been studied, she said. For example, in soldiers who have severe head wounds, many go on to develop epilepsy in the months after their injuries. "Maybe their injuries trigger the development of excess excitatory synaptic connections, and blocking or modulating this preemptively with gabapentin could help to prevent in this situation."

She said that understanding how the receptor works could also help patients who have neuropathic pain because of advanced diabetes or an injury.

"Neuropathic pain is not perceived by patients in the same way as other types of pain." Eroglu said. "Regular anti-analgesic drugs do not successfully ease this type of pain. Based on our findings it is possible that aberrant new synaptic connections that occur after injury contribute to neuropathic pain, and gabapentin might work by breaking this cycle of synapse formation."

The research was supported by grants from the National Institute of Drug Addiction, the National Heart, Lung and Blood Institute, the National Institutes of Health, the Human Frontiers Scientific Program long-term fellowships, and the Helen Hay Whitney postdoctoral fellowship.

The senior author of the work is Dr. Eroglu's mentor Ben A. Barres, of the Department of Neurobiology at Stanford University School of Medicine in Stanford, Calif.,. Other authors include Nicola J. Allen, Michael W. Susman, Chan Young Park, Chandrani Chakraborty, Sara B. Mulinyawe, Andrew D. Huberman, Eric M. Green, and Ricardo Dolmetsch, of the Stanford Department of Neurobiology; Jack Lawler, of the Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School in Boston; Nancy A. O'Rourke, Engin Özkan, K. Christopher Garcia, and Stephen J. Smith, all of the Department of Molecular and Cellular Physiology at Stanford (Özkan and Garcia are also in the Stanford Department of Structural Biology and Howard Hughes Medical Institute); Z. David Luo, of the Department of Anesthesiology & Perioperative Care, University of California, Irvine; Arnon Rosenthal, of MazoRx Inc., Redwood City, Calif.; and Deane F. Mosher and Douglas S. Annis of the Department of Medicine, Medical Sciences Center, University of Wisconsin, Madison.

Mary Jane Gore | 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 >>>