Featured Research

from universities, journals, and other organizations

Understanding Fragile X Syndrome With The Blink Of An Eye

Date:
August 4, 2005
Source:
Cell Press
Summary:
While researchers have long known the genetic defect underlying Fragile X syndrome, they are still tracing how that defect creates the complex mix of mental retardation, hyperactive behavior, attention deficits, and other problems in the disorder. Fragile X is particularly important because it is the most common single-gene cause of mental retardation -- affecting about 1 in 4000 males and 1 in 8000 females in the U.S.

While researchers have long known the genetic defect underlying FragileX syndrome, they are still tracing how that defect creates the complexmix of mental retardation, hyperactive behavior, attention deficits,and other problems in the disorder. Fragile X is particularly importantbecause it is the most common single-gene cause of mentalretardation--affecting about 1 in 4000 males and 1 in 8000 females inthe U.S.

In an article in the August 4, 2005, issue of Neuron,researchers led by Chris De Zeeuw of Erasmus University Rotterdamreport that they have pinpointed a specific cause of defects in motorlearning in Fragile X patients. Their work represents the firstinvestigation of the role of abnormalities in the brain's cerebellum inFragile X syndrome.

Fragile X syndrome is caused by a defect in the Fragile Xmental retardation 1 (Fmr1) gene, which in turns produces anonfunctioning protein, FMRP. In their studies, De Zeeuw and colleaguesstudied the behavioral effects on motor learning and the effects onneurons in the cerebellum of knocking out this gene.

They found that mice lacking the gene showed deficits in aparticular motor learning task known to be largely controlled by thecerebellum. In this "eyeblink conditioning" task, the mice were taughtto associate a stimulus such as a tone with a puff of air on their eye,and the blink response was measured as an indication of how well theanimals could learn the task. The researchers found that micecompletely lacking the Fmr1 gene showed deficits in the motor learningtask. But most importantly, the researchers also found that micelacking the Fmr1 gene only in specific neurons, called Purkinje cells,in the cerebellum showed the deficit.

Detailed electrophysiological studies of Purkinje cells in suchmutant mice revealed that the cells showed an enhanced weakening oftheir signaling connections--called long-term depression. Theresearchers also found that the Purkinje cells showed abnormalities instructures called dendrites, which are the branches from nerve cellsthat contain the receiving stations for signals from other neurons.

When the researchers conducted similar eyeblink conditioning tests in Fragile X patients, they found the same severe deficits.

And when the researchers created a mathematical model oflong-term depression, they found that they could link alteration insignaling between neurons in the cerebellum with impairment in motorlearning processes.

"Thus, while a lack of FMRP in areas such as the cerebralcortex, amygdala, and hippocampus may induce cognitive symptoms inFragile X syndrome, the current data allow us to conclude that a lackof functional FMRP in cerebellar P cells may equally well lead todeficits in motor learning in Fragile X patients," concluded theresearchers.

###

The researchers include S.K.E. Koekkoek, B.A. Milojkovic, B.R.Dortland, T.J.H. Ruigrok, W. De Graaf, A.E. Smit, F. VanderWerf, C.E.Bakker, R. Willemsen, E. Mientjes, M. Joosten, B.A. Oostra, and C.I. DeZeeuw of Erasmus MC, Rotterdam, The Netherlands; K. Yamaguchi,T. Ikeda,S. Kakizawa, K. Onodera, and M. Ito of RIKEN, Saitama, Japan; R. Maexand E. De Schutter of University of Antwerp, Belgium; and D.L. Nelsonof Baylor College of Medicine, Houston, Texas. This work was supportedby the Dutch Organization for Medical Sciences, Life Sciences,Neuro-Bsik consortium, and the European Community (EC). B.A.O.,S.K.E.K., and D.L.N. were supported by NIH and FRAXA ResearchFoundation. E.D.S. and R.M were supported by EC and IUAP and FWO(Belgium).

Koekkoek et al.: "Deletion of FMR1 in Purkinje Cells EnhancesParallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar EyelidConditioning in Fragile X Syndrome." Publishing in Neuron, Vol. 47,pages 339--352, August 4, 2005. DOI 10.1016/j.neuron.2005.07.005 www.neuron.org


Story Source:

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


Cite This Page:

Cell Press. "Understanding Fragile X Syndrome With The Blink Of An Eye." ScienceDaily. ScienceDaily, 4 August 2005. <www.sciencedaily.com/releases/2005/08/050804125012.htm>.
Cell Press. (2005, August 4). Understanding Fragile X Syndrome With The Blink Of An Eye. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2005/08/050804125012.htm
Cell Press. "Understanding Fragile X Syndrome With The Blink Of An Eye." ScienceDaily. www.sciencedaily.com/releases/2005/08/050804125012.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com
Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. 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