Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find potential cause of breathing problems in Rett Syndrome children

14.12.2005


A multi-institutional team, led by University of Chicago researchers, has taken a crucial step toward understanding and treating Rett syndrome (RS), a rare and often-misdiagnosed neurodevelopmental disorder that affects 1 in 10,000 children, mostly females.



In a study published in the Dec. 14, 2005, issue of the Journal of Neuroscience, the researchers describe in a mouse model for RS the source of erratic breathing, which has important implications for children with RS.

Along with breathing problems, RS causes slowed brain and head growth, mental retardation, seizures, gait abnormalities and handwringing.


"It is absolutely tragic for the family," said Jan-Marino Ramirez, professor of organismal biology and anatomy at Chicago and lead author of the paper. "It’s a progressive disease that shows no mercy."

In order to study the breathing pattern more closely, Ramirez and his team showed that mice with the RS gene exhibit the same behavior as children: They breathe irregularly and stop breathing often.

According to Ramirez, one hypothesis that has dominated the thinking of many clinicians is that the erratic breathing is due to cortical problems. "It’s as if they want to stop breathing," he said. "Some clinicians went that far to suggest that it could be pleasurable for the child to stop breathing all of the time because they get a euphoric high. Or they do this because they’re agitated."

However, the researchers traced the problem not to the cortex but to the breathing center itself--in the medulla. The researchers isolated the breathing center from mutant mice and were able to demonstrate that the same erratic breathing pattern, which is so characteristic for RS, also was expressed in the isolated brain tissue, revealing the breathing center as the source of the problem.


They also found, specifically in the breathing center, a significantly decreased amount of the neuromodulator norepinephrine.

When Ramirez’s team added norepinephrine to the isolated breathing center, the breathing pattern normalized. "It became exactly as regular as the control-- this was amazing," he said. "This experiment shows that the breathing problem can potentially be treated because you can compensate for the missing neuromodulatory drive."

While Ramirez’s team worked with the brain tissue, his colleagues in France studied the animal.

Although they found the disturbance specifically in the medulla, many of those neurons project to other targets in the brain, which may explain why many other functions are affected.

Researchers noted that the disturbance in the breathing rhythm of the tissue occurs early on, before the animal exhibits breathing problems. They suggest that the nervous system may compensate initially for the loss of norepinephrine, which may be why breathing appears normal at the behavioral level. However, the deficiency in norepinephrine eventually disturbs other neuromodulators, including serotonin and substance P. As other modulatory systems become disrupted there will be a cascade of physiological problems in the animal’s developmental and autonomic systems, including the obvious disturbances in the breathing behavior itself.

According to Ramirez, it is not known how the mutation on the MECP2 gene, which was linked to RS in 1999, leads to the disturbance of the norepinephrine. "This is obviously one of the next issues that needs to be addressed in our experiments."

Ramirez also plans to start screening medications already on the market to treat the erratic breathing of the animal model, looking specifically at those drugs that treat both neural systems: norepinephrine and serotonin. (Substance P also will be affected since it is located in the same nerve cells as serotonin.)

Prozac, for example, is often prescribed to treat depression by boosting serotonin levels, as well as other drugs currently are used for attention deficit hyperactivity disorder that boost both serotonin and norepinephrine levels.

Scientists are eager to discover whether treating the erratic breathing of RS will affect any of the other problems associated with the disorder.

"I think it’s going to have a wider effect," Ramirez said, "because norepinephrine, serotonin and substance P are not only involved in breathing control, they’re also involved in many other functions, including motor control, which may help with the handwringing or if we are lucky, possibly also their walking.

"The breathing center is just one of the disturbed functions," he added. "It’s the tell tale sign."

Ramirez also plans to further investigate why these neurons are not releasing enough norepinephrine. "By understanding any of these neuromodulators, you’ll better understand a lot of childhood disorders."

Texas scientists, headed by Huda Zoghbi, located the mutated RS gene, MECP2, on the X chromosome in 1999. Since females have two X chromosomes, the normal version of the gene can compensate for much of the dysfunction. For boys there is no compensation; males die young, within the first year of life.

Severity of RS can vary. In some, RS is so serious that the child can no longer talk, sit or walk. Many children with RS die before they reach their teenage years, and breathing abnormalities are thought to be the leading cause.

Catherine Gianaro | EurekAlert!
Further information:
http://www.uchospitals.edu

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>