Featured Research

from universities, journals, and other organizations

New clue found for Fragile X syndrome-epilepsy link

Date:
April 12, 2011
Source:
Emory University
Summary:
Individuals with fragile X syndrome, the most common inherited form of intellectual disability, often develop epilepsy, but so far the underlying causes are unknown. Researchers have now discovered a potential mechanism that may contribute to the link between epilepsy and fragile X syndrome.

Kv4.2, which regulates electrical signals, is lower in cells from mice missing FMRP ("KO") compared to wild-type ("WT").
Credit: Christina Gross

Individuals with fragile X syndrome, the most common inherited form of intellectual disability, often develop epilepsy, but so far the underlying causes are unknown. Researchers have now discovered a potential mechanism that may contribute to the link between epilepsy and fragile X syndrome.

The protein that is missing in fragile X syndrome, FMRP, controls the production of a protein that regulates electrical signals in brain cells, scientists at Emory University School of Medicine have found. The results were published April 13 in the Journal of Neuroscience.

Individuals with fragile X syndrome tend to have a hyperexcitable nervous system, which can be displayed in several ways: hyperactivity, anxiety, increased sensory sensitivity, and epileptic seizures in 20 percent of all cases. The Emory team's findings suggest that a therapeutic strategy against fragile X syndrome now being tested in clinical trials could also address this aspect of the disease.

"The link between fragile X syndrome and epilepsy was not well understood," says senior author Gary Bassell, PhD, professor of cell biology and neurology at Emory University School of Medicine. "This finding might provide a molecular explanation that could also give some clues on therapeutic strategies."

The co-first authors of the paper are postdoctoral fellow Christina Gross and PhD candidate Xiaodi Yao. They and their colleagues found that in mice missing FMRP -- a model for humans with fragile X syndrome -- brain cells produce less of a protein called Kv4.2.

FMRP is known to regulate several genes, and it's possible that changes in others besides Kv4.2 contribute to the development of epilepsy. For many of the genes that FMRP controls, it normally acts as a brake, by interfering with the step in which RNA is made into protein. In FMRP's absence, this leads to runaway protein production at synapses the junctions between brain cells where chemical communication occurs. Kv4.2 appears to be an exception, because in FMRP's absence, less Kv4.2 protein is produced.

The protein Kv4.2 is an ion channel, which allows electrical charge to flow out of neurons when they are stimulated. Kv4.2 is the major ion channel regulating the excitability of neurons in the hippocampus, a region of the brain important for learning and memory. A mutation of the gene encoding Kv4.2 leads to temporal lobe epilepsy in humans.

In laboratory tests, drugs that tamp down glutamate signaling could partially restore levels of the Kv4.2 protein in mice missing the fragile X protein. This suggests that drugs that act against glutamate signaling, which are now in clinical trials, could reduce hyperexcitability in humans with fragile X syndrome.

Another strategy could be to identify drugs that target the Kv4.2 protein's function directly, Bassell says.

Not all individuals with fragile X syndrome develop epilepsy. The loss of FMRP doesn't shut Kv4.2 production off completely, and other genetic variations and environmental factors probably contribute to the development of epilepsy in individuals with fragile X syndrome, Bassell says.

The research was supported by the National Institutes of Health and the National Fragile X Foundation.

Reference:

C. Gross*, X. Yao*, D.L. Pong, A. Jeromin and G.J. Bassell. Fragile X Mental Retardation Protein Regulates Protein Expression and mRNA Translation of the Potassium Channel Kv4.2. J. Neurosci, 31, pa


Story Source:

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


Cite This Page:

Emory University. "New clue found for Fragile X syndrome-epilepsy link." ScienceDaily. ScienceDaily, 12 April 2011. <www.sciencedaily.com/releases/2011/04/110412171202.htm>.
Emory University. (2011, April 12). New clue found for Fragile X syndrome-epilepsy link. ScienceDaily. Retrieved April 21, 2014 from www.sciencedaily.com/releases/2011/04/110412171202.htm
Emory University. "New clue found for Fragile X syndrome-epilepsy link." ScienceDaily. www.sciencedaily.com/releases/2011/04/110412171202.htm (accessed April 21, 2014).

Share This



More Health & Medicine News

Monday, April 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Breakfast Foods Are Getting Pricier

Breakfast Foods Are Getting Pricier

AP (Apr. 21, 2014) Breakfast is now being served with a side of sticker shock. The cost of morning staples like bacon, coffee and orange juice is on the rise because of global supply problems. (April 21) Video provided by AP
Powered by NewsLook.com
Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
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:
from the past week

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