PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Fragile X makes brain cells talk too much

2013-02-20
(Press-News.org) The most common inherited form of mental retardation and autism, fragile X syndrome, turns some brain cells into chatterboxes, scientists at Washington University School of Medicine in St. Louis report.

The extra talk may make it harder for brain cells to identify and attend to important signals, potentially establishing an intriguing parallel at the cellular level to the attention problems seen in autism.

According to the researchers, understanding the effects of this altered signaling will be important to developing successful treatments for fragile X and autism.

"We don't know precisely how information is encoded in the brain, but we presume that some signals are important and some are noise," says senior author Vitaly Klyachko, PhD, assistant professor of cell biology and physiology. "Our theoretical model suggests that the changes we detected may make it much more difficult for brain cells to distinguish the important signals from the noise."

The findings appear Feb. 20 in Neuron.

Fragile X is caused by mutations in a gene called Fmr1. This gene is found on the X chromosome, one of the two sex chromosomes. Females have two copies of that chromosome, while males only have one. As a result, males have fragile X syndrome more often than females, and the effects in males tend to be more severe.

Symptoms of fragile X include mental retardation, hyperactivity, epilepsy, impulsive behavior, and delays in the development of speech and walking. Fragile X also affects anatomy, leading to unusually large heads, flat feet, large body size and distinctive facial features. Thirty percent of fragile X patients are autistic.

Scientists deleted the Fmr1 gene many years ago in mice to create a model of fragile X. Without Fmr1, the mice have abnormalities in brain cells and social and behavioral deficits similar to those seen in human fragile X.

According to Klyachko, nearly all fragile X mouse studies in the past two decades have focused on how Fmr1 loss affects dendrites, the branches of nerve cells that receive signals. In contrast, his new study finds significant changes in axons, the branches of nerve cells that send signals.

Normally, signals travel down the axon as surges of electrical energy. These surges only last for tiny fractions of a second, briefly causing the axon to release compounds known as neurotransmitters into the short gap between nerve cells. The neurotransmitters cross the gap and bind to their receptors on the dendrite to convey the signal.

When Klyachko monitored electrical surges along axons in the fragile X mice, though, he discovered that they lasted significantly longer. This caused release of more of neurotransmitters from the axon. When it should have stopped talking, the axon continued to chatter.

"The axons are putting out much more neurotransmitter than they should, and we think this confuses the system and overloads the circuitry," Klyachko explains. "It may also create problems in terms of brain cells using up their resources much more quickly than they normally would."

Infusing synthetic copies of the gene's protein, called FMRP, into brain cells from the mouse model rapidly restored the electrical surges to their normal length.

Additional experiments revealed that FMRP works by interacting with one of the biggest channels on the surfaces of axons. These channels let electrically charged potassium ions into the axons, helping to shape and control the duration of the electrical surge.

In healthy brain cells, the main function of these channels is to prevent the electrical surge from getting too long. With FMRP gone, the channel is active for a shorter time, prolonging the surge and overwhelming the dendrite with too much chatter.

Klyachko and his colleagues are now studying the connections between FMRP and the channel it interacts with in axons. They hope to learn more about how information is encoded and processed at the level of individual brain cells. These insights one day may help clinicians better diagnose and treat many kinds of mental disorders.

###

Deng P-Y, Rotman Z, Blundon JA, Cho Y, Cui J, Cavalli V, Zakharenko SS, Klyachko VA. FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels. Neuron, Feb. 20, 2013.

Funding from the National Institute of Neurological Disorders and Stroke (R01 NS081972, RO1 NS060709 and R01 NS060706), FRAXA Foundation, the Edward Mallinckrodt Foundation, the McDonnell Center for Systems Neuroscience, and the National Institutes of Mental Health (R01 MH079079 and R01 MH095810).

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

END



ELSE PRESS RELEASES FROM THIS DATE:

Cost of medication and stigma leading asthma sufferers to risk health

2013-02-20
The high cost of medication, stigmatisation and poor acceptance of their condition are causing young adults to take a dangerous approach to managing their asthma, according to new research published today in the journal BMJ Open. In the UK 5.4 million people are currently receiving treatment for asthma: 1.1 million children (one in 11) and 4.3 million adults (one in 12). There were 1,131 deaths from asthma in the UK in 2009. Most asthma deaths are preventable. Despite the availability of effective treatments, poor asthma control is common. The overuse of short-acting ...

Simple measures to promote sleep can reduce delirium in intensive care patients

2013-02-20
A hospital is not the best place to get a good night's sleep, especially in a noisy intensive care unit. It's a cause for concern because studies have shown that a lack of sleep can cause patients to experience delirium—an altered mental state that may delay their recovery and lead to short and long-term confusion and memory problems. A team of doctors, nurses, psychologists and pharmacists in the medical intensive care unit (MICU) at The Johns Hopkins Hospital implemented a project to see if by taking simple steps to reduce nighttime noise, light,and staff interruptions, ...

Tool boosts success of online collaborations by redistributing the burdens of leadership

2013-02-20
PITTSBURGH—The Web makes it possible for lots of people to collaborate on projects, but it doesn't make it easy to lead them. A Carnegie Mellon University researcher has developed a new tool that helps leaders see complex, collaborative projects through to completion by redistributing leadership responsibilities. The tool, called Pipeline, makes it easier to assign, critique and track the progress of individual tasks within a project and makes it easy for leaders to delegate responsibility to others. As evidenced by a case study in which Pipeline was used to manage the ...

First signals from brain nerve cells with ultrathin nanowires

2013-02-20
Electrodes operated into the brain are today used in research and to treat diseases such as Parkinson's. However, their use has been limited by their size. At Lund University in Sweden, researchers have, for the first time, succeeded in implanting an ultrathin nanowire-based electrode and capturing signals from the nerve cells in the brain of a laboratory animal. The researchers work at Lund University's Neuronano Research Centre in an interdisciplinary collaboration between experts in subjects including neurophysiology, biomaterials, electrical measurements and nanotechnology. ...

Researchers decipher modus operandi of potential Alzheimer's drug

2013-02-20
This press release is available in German. The study published in "Angewandte Chemie" might help to work out strategies for developing potential drugs. As the team of scientist including Markus Zweckstetter and Eckhard Mandelkow report, methylene blue inactivates molecular residues that promote the bonding of tau proteins. Methylene blue is a multi-talented substance with a long history. The synthetic compound was first produced in 1876, and since then has served not only as a blue dye, but also as a medical drug – for example to treat malaria and prevent urinary ...

Bilingual children have a better 'working memory' than monolingual children

Bilingual children have a better working memory than monolingual children
2013-02-20
A study conducted at the University of Granada and the University of York in Toronto, Canada, has revealed that bilingual children develop a better working memory –which holds, processes and updates information over short periods of time– than monolingual children. The working memory plays a major role in the execution of a wide range of activities, such as mental calculation (since we have to remember numbers and operate with them) or reading comprehension (given that it requires associating the successive concepts in a text). The objective of this study –which was published ...

Healthy rivalry could boost sport and business performance

Healthy rivalry could boost sport and business performance
2013-02-20
New research shows that people can recover from poor performance when rivals comment on their failures. The research, to be published in the Journal of Experimental Social Psychology, shows that while criticism from team members sends individuals into downward performance spirals, external criticism can be a trigger that boosts performance as people try to prove the outsiders wrong. The research carried out by the University of Exeter, Amherst College and the University of Stirling offers a method of improving performance following setbacks and can be applied both in the ...

New taxonomy of platinum nanoclusters

2013-02-20
Physicists have gained new insights into the inner intricacies of the structural variations of metallic nanoclusters. This work by Luca Pavan, Cono Di Paola and Francesca Baletto from King's College London, UK, is about to be published in EPJ D. It takes us one step closer to tailoring on-demand characteristics of metallic nanoparticles. Indeed, the geometric structure of these nanoclusters influences their chemical and physical properties, which differ from those of individual molecules and of bulk metals. The problem resides in the difficulty in evaluating the optimal ...

Molecular basis identified for tissue specific immune regulation in the eye and kidney

2013-02-20
Both AMD, which affects around 50 million people worldwide, and aHUS, a rare kidney disease that affects children, are associated with incorrectly controlled immune systems. A protein called complement factor H (CFH) is responsible for regulating part of our immune system called the complement cascade. Genetic alterations in CFH have been shown to increase a person's risk of developing either AMD or aHUS, but rarely both. Why this is the case has never been explained until now. Researchers from the Wellcome Trust Centre for Cell Matrix Research and the Ophthalmology and ...

The nano-channel that disentangles knots

The nano-channel that disentangles knots
2013-02-20
The DNA, just like hair, has a tendency to become knotted, thus it may be useful to disentangle it. Unfortunately, it is not possible to "actively" choose at random (or better, in one solution) the filaments with the desired features, and this is why scientists adopt "passive" solutions like, for instance, having the DNA pass through nano-pores or nano-channels. "Channels and filaments have physical features we may exploit to selectively let a type of molecule pass through" explains Micheletti. "You can have more or less entangled filaments and featuring knots of different ...

LAST 30 PRESS RELEASES:

Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker

Chips off the old block

Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia

Cutting the complexity from digital carpentry

Lung immune cell type “quietly” controls inflammation in COVID-19

Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity

State and sociodemographic trends in US cigarette smoking with future projections

Young adults drive historic decline in smoking

NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Chimpanzee stem cells offer new insights into early embryonic development

This injected protein-like polymer helps tissues heal after a heart attack

FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology

In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity

Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects

A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions

AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate

Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative

Structure dictates effectiveness, safety in nanomedicine

Mission accomplished for the “T2T” Hong Kong Bauhinia Genome Project

Study identifies how malaria can lead to childhood cancer

An earth-abundant mineral for sustainable spintronics

What makes successful learners? How Minecraft can helps us understand social learning

Researchers create ‘super stem cells’, seeing potential for improved fertility treatment

Empathic comforting varies more within bonobo and chimpanzee species than between them

AACR 2025: Colon cancer risk reduction, predicting melanoma spread and new drug therapies among Ohio State findings

Landmark 20-year screening program drives down colorectal cancer cases, deaths

Can a baby’s DNA predict future disease? This study says it might

Gene mutations linked to worse outcomes in stomach cancer

Blood proteins can predict liver disease up to 16 years before symptoms

Study: New DNA-reading technology holds promise for rare disease research

[Press-News.org] Fragile X makes brain cells talk too much