Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

14.10.2009
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:
http://www.duke.edu

More articles from Life Sciences:

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>