Featured Research

from universities, journals, and other organizations

New fruit fly model of epilepsy reveals mechanisms behind fever-induced seizures

Date:
October 17, 2012
Source:
University of California - Irvine
Summary:
Researchers have created a new fruit fly model of inherited epilepsy that's providing insights into the mechanisms underlying temperature-dependent seizures while establishing a platform from which to develop therapies for these disorders.

UC Irvine and Brown University researchers have created a new fruit fly model of inherited epilepsy that's providing insights into the mechanisms underlying temperature-dependent seizures while establishing a platform from which to develop therapies for these disorders.

In the Oct. 10 issue of The Journal of Neuroscience, Diane O'Dowd of UCI, Robert Reenan of Brown and colleagues report their method for placing a gene mutation that causes human fever-induced seizures into drosophila fruit flies. As a result, the mutant flies experience heat-induced seizures.

This represents the first time a human genetic disease mutation has been "knocked in" to the equivalent location in the fruit fly genome. The drosophila knock-in model provides a rapid and low-cost basis for defining the neural mechanisms contributing to inherited seizure disorders.

"We can also use this genetic model of human epilepsy in fruit flies to look for new treatments for the disease," said O'Dowd, professor and chair of developmental & cell biology at UCI.

Fever-induced, or febrile, seizures are most commonly seen in children. Only about one in 100 children with febrile seizures develops epilepsy, and most outgrow them by age 5. In contrast, individuals who have the inherited disorder -- termed GEFS+ -- have febrile seizures that persist beyond childhood and also often develop seizures in the absence of fever.

Reenan, a biology professor at Brown, and Brown undergraduate Jeff Gilligan used a genetic-exchange research method called "homologous recombination" to insert a mutation into the gene in fruit flies that's a direct parallel of the GEFS+ mutation in the human SCN1A sodium channel gene that causes febrile seizures in people.

When placed in tubes that were put in warm water, most of the mutant fruit flies began to experience seizures within 20 to 30 seconds. They would fall over, and their wings would flap and their legs twitch for about two minutes while the flies were kept at a high temperature. The researchers found that seizure susceptibility was dose-dependent: Ninety-five percent of the flies with two copies of the mutant gene had seizures, as opposed to 60 percent of those with just one copy. Unaltered control flies did not have temperature-dependent seizures.

To determine the neurological causes of the seizures, O'Dowd, her postdoctoral fellow and lead study author Lei Sun, and UCI colleagues examined neurons in the brains of both mutant and control flies to monitor activity and see how they behaved as the brains were heated. In the mutant flies, they discovered flaws in the functioning of sodium channels.

"What happens is the mutant channels don't open and close properly," O'Dowd said. "This effect is amplified at high temperature, and this changes the ability of neurons to generate the appropriate electrical signals, leading to hyperactivity in the brain circuits."

"With this knowledge, the next step is to use this model to look for drugs that might reduce or eliminate heat-induced seizures," she added.

In addition to providing insight into the neurology of febrile seizures, the study establishes a new fruit fly model as a viable genetic platform for the study of epilepsy and validates the use of homologous recombination in flies to explore mechanisms underlying other genetically linked diseases.

Ryan Schutte and Vivian Nguyen of UCI and Cynthia Staber of Brown also contributed to the study, which was funded by the National Institutes of Health, Howard Hughes Medical Institute and the Ellison Medical Foundation.


Story Source:

The above story is based on materials provided by University of California - Irvine. Note: Materials may be edited for content and length.


Journal Reference:

  1. L. Sun, J. Gilligan, C. Staber, R. J. Schutte, V. Nguyen, D. K. O'Dowd, R. Reenan. A Knock-In Model of Human Epilepsy in Drosophila Reveals a Novel Cellular Mechanism Associated with Heat-Induced Seizure. Journal of Neuroscience, 2012; 32 (41): 14145 DOI: 10.1523/JNEUROSCI.2932-12.2012

Cite This Page:

University of California - Irvine. "New fruit fly model of epilepsy reveals mechanisms behind fever-induced seizures." ScienceDaily. ScienceDaily, 17 October 2012. <www.sciencedaily.com/releases/2012/10/121017141813.htm>.
University of California - Irvine. (2012, October 17). New fruit fly model of epilepsy reveals mechanisms behind fever-induced seizures. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2012/10/121017141813.htm
University of California - Irvine. "New fruit fly model of epilepsy reveals mechanisms behind fever-induced seizures." ScienceDaily. www.sciencedaily.com/releases/2012/10/121017141813.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins